Systems and methods comprising linked localization agents

ABSTRACT

Provided herein are systems and methods comprising two or more localization agents that are linked together by a linker. For example, provided herein are systems and methods for the placement of two or more linked localization devices within biological systems and the detection of such localization devices for targeted surgeries or other medical procedures. For example, provided herein are systems comprising one or more miniature detectable devices that are linked together, that are placed into a target location and activated by remote introduction of a magnetic field.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication No. 63/078,971 filed on Sep. 16, 2020, the contents of whichare hereby incorporated by reference in their entirety.

FIELD

Provided herein are systems and methods comprising two or morelocalization agents that are linked together by a linker. For example,provided herein are systems and methods for the placement of two or morelinked localization devices within biological systems and the detectionof such localization devices for targeted surgeries or other medicalprocedures. For example, provided herein are systems comprising one ormore miniature detectable devices that are linked together, that areplaced into a target location and activated by remote introduction of amagnetic field.

BACKGROUND

A common and serious challenge for many medical procedures is theaccurate localization of treatment areas. For example, the location oflesions, such as tumors that are to undergo treatment, includingsurgical resection, continues to present a challenge to the medicalcommunity. Existing systems are expensive, complex, time-consuming, andoften unpleasant for the patient.

Recent methods for tissue localization for medical procedures involvethe use of localization agents, such as RFID tags, that may be placedwithin the patient. However, these tags may migrate within the patientin between placement and the performance of the surgical procedure,leading to a failure to properly mark the desired location within thepatient. Furthermore, the orientation of the tags may shift afterplacement within the patient, leading to a loss of accuracy inidentifying the 3-dimensional location of the tag within the patient.Additional problems with efficacy may arise with larger patients, wherethe strength of signal generated by a single tag is insufficient to bedetected due to the volume of tissue present.

Accordingly, improved systems and methods are needed for tissuelocalization for medical procedures.

SUMMARY

Provided herein are systems and methods comprising two or morelocalization agents (e.g. “tags”) that are linked together by a linker.For example, provided herein are systems and methods for the placementof two or more linked tags within biological systems and the detectionof such tags for targeted surgeries or other medical procedures. Whilethe description below illustrates the invention using examples of humansurgical procedures, it should be appreciated that the invention is notso limited and includes veterinary applications, agriculturalapplications, industrial applications, mechanical applications, militaryapplications (e.g., sensing and removal of dangerous materials from anobject or region), aerospace applications, and the like.

In some embodiments, provided herein are systems comprising one or moreof each of: a) at least two tags, b) a linker attached to each of the atleast two tags; c) a remote activating device (e.g., exciter assembly)that generates a magnetic field (e.g., time varying magnetic field)within a region of each tag, and d) a plurality of sensors configured todetect a signal from the at least two tags when the tags are exposed tothe magnetic field.

Each of the at least two tags are attached to at least one other tag(e.g. linked) by a linker. Tags connected to each other by a linker arereferred to herein as “linked tags”.

In some embodiments, the linker is a flexible linker. In someembodiments, the linker comprises plastic. In other embodiments, thelinker comprises a shape-memory alloy. For example, the linker maycomprise a nickel-titanium alloy (e.g., Nitinol 60 or Nitinol 55).

In some embodiments, the at least two tags are positioned to form anangle within a range of 15 degrees to 40 degrees. In some embodiments,the angle is 25 degrees.

In some embodiments, the linker includes a grip that is graspable by asurgical tool. In some embodiments, the grip is a sphere. In someembodiments, the linker is positioned within a packaging that includes anotch that exposes the grip.

In some embodiments, the linker comprises a torsion spring. In someembodiments, each of the tags is attached to the linker via heat shrinktubing.

In some embodiments, the linker is configured to hold the at least twotags in a first position when the tags are present in an insertiondevice. In some embodiments, the linker is configured to hold the atleast two tags in a second position when present in tissue, wherein atleast one of the tags in the second position points approximately in theX dimension, and at least one of the tags points approximately in the Ydimension. In some embodiment, the at least two tags comprises first,second, and third tags. In such embodiments, in said second position: i)said first tag points approximately in the X dimension, ii) said secondtag points in approximately the Y dimension, and iii) and said third tagpoints in approximately in the Z dimension.

In some embodiments, the system further comprises a wire or a line. Thewire or line may be attached to, and/or pass through, the linker at twoor more points on the linker. For example, the wire or line may beattached to, and/or pass through, the linker such that the two or moretags are held in a first position with respect to each other. The linkermay be configured to hold the two or more tags in a second position whenthe wire or line is not attached to, and/or does not pass through, thelinker. The second position may be different from the first position.

In some embodiments, the tags are programmed to respond to a signal fromthe magnetic field with an offset frequency compared to the signal. Insome embodiments, the tags comprise a non-dielectric resonant antennacapacitor.

In some embodiments, each of the at least two tags comprise an antenna,wherein each tag emits sidebands at defined frequencies upon activationby a magnetic field. In some embodiments, each tag antenna comprises acoil antenna. For example, each coil antenna may comprise a ferrite-corecoil antenna.

In some embodiments, each coil antenna resonates at 100-200 kHz. Eachcoil antenna may resonate at the same or substantially the samefrequency. Alternatively, each coil antenna may resonate at a differentfrequency.

In some embodiments, the remote activating device comprises at least oneexcitation coil. In some embodiments, the remote activating devicecomprises two or more excitation coils configured to flow current ineither a clockwise or counterclockwise direction such that the magneticfield generated by the remote activating device may be selectivelygenerated in one or more of X, Y, and Z directions, (e.g., to ensurethat the tags can be excited for multiple or any angle that it may beplaced). In some embodiments, the magnetic field is generated in two ormore of X, Y, and Z directions. In some embodiments, the magnetic fieldis generated in each of the X, Y, and Z directions.

In some embodiments, the remote activating device comprises four or moreexciter coils. In some embodiments, the exciter coils are connected inseries. In some embodiments, four of the exciter coils are in a layoutof two rows centered at coordinates (X1, Y1), (X1, Y2), (X2, Y1), and(X2, Y2). In some embodiments, the remote activating device (e.g.,exciter assembly) comprises at least one of three current flowconfigurations: a) all current clockwise to simulate an exciter coilaligned with a direction normal to the Z axis; b) exciter coils centeredat (X2, Y1), (X2, Y2) running current counter-clockwise to simulate anexciter coil aligned to the X axis; and c) exciter coils centered at(X1, Y2), (X2, Y2) running current counter-clockwise to simulate anexciter coil aligned substantially to the Y axis. In some embodiments,the remote activating device comprises all three of the above currentflow configurations.

In some embodiments, the remote activating device (e.g., exciterassembly) comprises a plurality of relays that provide a switchingfunction to accomplish the current direction change (polarity) yetmaintain an excitation frequency by switching additional capacitivereactance. In some embodiments, the switching function insertsadditional series capacitive reactance via a capacitance element whentotal inductance is increased so that a tuning center frequency ismaintained at said excitation frequency (e.g., the total inductance ofthe 4 coils, when 4 coils are employed, varies as the current directionis changed within each coil or coil pair). In some embodiments, thecapacitance element is comprised of multiple capacitors (e.g., to betteraccommodate the voltage potential at resonance and/or to provide greaterflexibility on frequency tuning). In some embodiments, the remoteactivating device further comprises a balun in proximity to the excitercoils. The balun eliminates common mode current that would otherwiseproduce unwanted electric field components that could otherwise reduceaccuracy. It also provides impedance transformation to match the realcomponent of the coil impedance to that of the transmission line,typically 50 Ohms. In some embodiments, the balun has eight turns on aprimary side (amplifier side) and four turns on a secondary side (coilside). In some embodiments, the system further comprises an amplifier inelectronic communication with the remote activating device. In someembodiments, the system further comprises a computer that controlsmagnetic field generation and sensor detection. In some embodiments, thecomputer comprises a hunting algorithm (e.g., embodied in softwarerunning on the processor) that adjusts the magnetic field orientation toidentify (and power) optimal detection of at least two tags.

Also provided herein are uses of any of the above systems (e.g., fordetecting the positions of two or more linked tags in an object; fordetecting a position of two or more linked tags relative to a medicaldevice; etc.).

Further provided herein are methods of identifying a position of two ormore linked tags, comprising: a) providing any of the systems describedherein; b) placing the at least two tags in an object; c) generating amagnetic field with the activating device; and d) identifying a positionof the tags in said object by collecting information emitted from eachtag with the witness stations. In some embodiments, the position orcomprises relative location or distance of the tags to a medical device.

In some embodiments, placing the at least two tags in an objectcomprises positioning the at least two tags into said object using anintroduction device. In some embodiments, the at least two tags arearranged in a first position within said introduction device. In someembodiments, the at least two tags migrate into a second position whenplaced in said object. In some embodiments, at least one of said tags insaid second position points approximately in the X dimension, and atleast one of said tags points approximately in the Y dimension. In someembodiments, the at least two tags comprises first, second, and thirdtags, and wherein, when in said second position: i) said first tagpoints approximately in the X dimension, ii) said second tag points inapproximately the Y dimension, and iii) and said third tag points inapproximately in the Z dimension.

Definitions

As used herein, the terms “processor” and “central processing unit” or“CPU” are used interchangeably and refer to a device that is able toread a program from a computer memory (e.g., ROM or other computermemory) and perform a set of steps according to the program.

As used herein, the terms “computer memory” and “computer memory device”refer to any storage media readable by a computer processor. Examples ofcomputer memory include, but are not limited to, RAM, ROM, computerchips, digital video discs (DVD), compact discs (CDs), hard disk drives(HDD), optical discs, and magnetic tape. In certain embodiments, thecomputer memory and computer processor are part of a non-transitorycomputer (e.g., in the control unit). In certain embodiments,non-transitory computer readable media is employed, where non-transitorycomputer-readable media comprises all computer-readable media with thesole exception being a transitory, propagating signal.

As used herein, the term “computer readable medium” refers to any deviceor system for storing and providing information (e.g., data andinstructions) to a computer processor. Examples of computer readablemedia include, but are not limited to, DVDs, CDs, hard disk drives,magnetic tape and servers for streaming media over networks, whetherlocal or distant (e.g., cloud-based).

As used herein, the term “in electronic communication” refers toelectrical devices (e.g., computers, processors, etc.) that areconfigured to communicate with one another through direct or indirectsignaling. Likewise, a computer configured to transmit (e.g., throughcables, wires, infrared signals, telephone lines, airwaves, etc.)information to another computer or device, is in electroniccommunication with the other computer or device.

As used herein, the term “transmitting” refers to the movement ofinformation (e.g., data) from one location to another (e.g., from onedevice to another) using any suitable means.

As used herein, the term “alloy” refers to a combination of a metal withat least one other metal or nonmetal. The term “shape-memory alloy”refers to an alloy that can be deformed when cold but returns to it'spre-deformed (e.g. “remembered”) shape when heated.

As used herein, the term “subject” or “patient” refers to any animal(e.g., a mammal), including, but not limited to, humans, non-humanprimates, companion animals, livestock, equines, rodents, and the like,which is to be the recipient of a particular treatment. Typically, theterms “subject” and “patient” are used interchangeably herein inreference to a human subject.

As used herein, the term “subject/patient suspected of having cancer”refers to a subject that presents one or more symptoms indicative of acancer (e.g., a noticeable lump or mass) or is being screened for acancer (e.g., during a routine physical). A subject suspected of havingcancer may also have one or more risk factors. A subject suspected ofhaving cancer has generally not been tested for cancer. However, a“subject suspected of having cancer” encompasses an individual who hasreceived an initial diagnosis (e.g., a CT scan showing a mass) but forwhom the stage of cancer is not known. The term further includes peoplewho once had cancer (e.g., an individual in remission).

As used herein, the term “biopsy tissue” refers to a sample of tissue(e.g., breast tissue) that is removed from a subject for the purpose ofdetermining if the sample contains cancerous tissue. In someembodiments, biopsy tissue is obtained because a subject is suspected ofhaving cancer. The biopsy tissue is then examined (e.g., by microscopy;by molecular testing) for the presence or absence of cancer.

As used herein, the term “linker” herein refers to a suitable materialwhich connects one tag to another tag. The linker may comprise anysuitable material. For example, the linker may comprise plastic.Alternatively, the linker may comprise a shape-memory alloy. As usedherein, the term “linked tags” refers to a group of at least two tags,wherein at least one tag is attached to at least one other tag via alinker. The term may refer to two attached tags. The term may refer tothree or more tags, wherein each tag is attached to at least one othertag via one or more linkers.

As used herein, the term “tag” or “marker tag” refers to the smallimplantable marker that, when excited by an exciter's time varyingmagnetic field, will emit a “homing beacon” spectrum of frequency(ies)received by the witness coil(s) and used to determine its location. Itmay be programmed to produce a unique spectrum, thus permitting multipletags to be implanted and located simultaneously.

DESCRIPTION OF DRAWINGS

FIG. 1 shows an exemplary positioning of an exciter assembly, a medicaldevice with display component attached, and a patient with a tagimplanted next to a tumor.

FIG. 2 shows an attachment component 10 that is attached to a medicaldevice 20, which has a device tip 25. The attachment component 10 hastwo location emitters 70 located therein. The attachment component 10 isattached to, or integral, with a display component 40.

FIG. 3 shows an exemplary coil configuration of an exciter assembly.

FIG. 4A shows an exemplary exciter assembly 250 attached to controller210 via a cable bundle 200. FIG. 4B shows an exemplary witness coilassembly (aka witness station assembly) 161. FIG. 4C shows an exemplarywitness coil 160, including the three directions in which wire is woundto form coils 167 over the metal core 166.

FIG. 5 shows an exemplary exciter assembly with four exciter coils(Coils A-D), where the current is flowing in the clockwise direction inall four exciter coils.

FIG. 6 shows an exemplary exciter assembly with four exciter coils(Coils A-D), where the current is flowing in the clockwise direction inCoils A and B, and flowing in the counterclockwise direction in Coils Cand D.

FIG. 7 shows an exemplary exciter assembly with four exciter coils(Coils A-D), where the current is flowing in the clockwise direction inCoils A and C, and flowing in the counterclockwise direction in Coils Band D.

FIG. 8 shows an exemplary exciter assembly 250 with the top cover 230on. The exciter assembly 250 is shown with cable bundle 200 leadingtherein.

FIG. 9 shows an exemplary attachment component 10, with an angled distalend 300 that the distal tip 25 of the medical device 20 is insertedthrough.

FIG. 10A shows the distal end 25 of a medical device 20 after it isinitially inserted through the angled distal end 300 of attachmentcomponent 10. FIG. 10B shows attachment component wire 60 prior to beingattached to the cable management component 315 of the display componenthousing 330. FIG. 10B shows attachment component wire 60 prior to beingattached to the cable management component 315 of the display componenthousing 330. FIG. 10B also shows the housing tapered connection 340 thatthe proximal end tapered connection 350 of the attachment component 10is inserted into. The cable management component 315 has two clips thatattached to and align both the attachment component wire 60 and themedical device wire 50.

FIG. 11 shows an exemplary attachment component 10 attached to a displaycomponent housing 330. The attachment component 10 has a pair oflocation emitters 70, which are linked to location emitter wires leads72 which are inside tube 360. The attachment component also has anangled distal end 300 with a distal end opening 305, which allows thetip of a surgical or other device to be inserted therethrough. Thedisplay component housing 330 has a cable management component 315,composed of a pair of clips for holding insulated wires.

FIG. 12 shows an exemplary attachment component 10 attached to a displaycomponent housing 330 with a display component 40 located therein. Adisplay cover 370 is shown, which is used to secure the displaycomponent 40 inside the display component housing 330. Also shown is anadhesive strip 380, which is shaped and sized to fit inside theattachment component and help secure a medical device to the attachmentcomponent.

FIG. 13A shows the proximal end tapered connection 350 of the attachmentcomponent 10, which is configured to push-fit into housing taperedconnection 340 of the display component housing 330. FIG. 13B shows aclose up of section A of FIG. 13A, including cable management taperedconnection 317 that is part of cable management component 315 anddesigned to be inserted into tapered connection hole 319 of displaycomponent housing 330. Cable management tapered connection 317 includesa flat part 318 to lock angular position.

FIG. 14 shows an exemplary system for localizing a tag that is implantedin a patient. The system is composed of an exciter assembly that emitssignals that activate the tag(s) in the patient. A systems electronicsenclosure is shown as a mobile cart, which delivers signals to theexciter assembly and receives and processes signals from the tag(s) inthe patient. Guidance for a surgeon is displayed on the displaycomponent, as well as on a screen on the systems electronics enclosure.

FIG. 15 shows an exemplary arrangement of two tags connected by aNitinol linker.

FIG. 16 shows an exemplary arrangement of two tags connected by aNitinol linker and a wire or line containing crimps and a self-cinchingwasher.

FIG. 17 shows an exemplary arrangement of two tags connected by alinker.

FIG. 18 shows the arrangement of FIG. 17 in a packaging.

DETAILED DESCRIPTION

Provided herein are systems, devices, assemblies, and methods forlocalization two or tags connected by a linker, for example, in a tissueof a patient. For example, provided herein are systems, devices, andmethods employing one or more or all of: a) two or more linked tagsplaced into an object, such as a patient; b) a remote activating devicethat generates an electromagnetic field within a region of the tags; c)a plurality of sensors (e.g. witness stations) that receive informationfrom the tags that have been exposed to the electromagnetic field; d)one or more emitters positioned on a medical device that are exposed tothe electromagnetic field and that emit information received by thesensors (e.g. witness stations); and e) a computer system for analyzinginformation received by the sensors and generating and displayinginformation about the positions of the medical device and/or tag or tags(e.g., relative location, relative distance, orientation, etc.).

The systems, devices, assemblies, and methods find use in a variety ofapplication including medical applications for locating the linked tagsin a subject. While the specification focuses on medical uses in humantissues, it should be understood that the systems and methods findbroader use, including non-human uses (e.g., use with non-human animalssuch as livestock, companion animals, wild animals, or any veterinarysettings). For example, the system may be used in environmentalsettings, agricultural settings, industrial settings, or the like. Insome embodiments, the systems, devices, assemblies, and methods find usein electromagnetic navigation systems that power a remote tag devicewith a sinusoidal magnetic field (see e.g., U.S. Pat. No. 9,730,764 andU.S. application Ser. Nos. 15/281,862 and 15/674,455, hereinincorporated by reference in their entireties).

In some embodiments, provided herein are systems comprising at least twotags, wherein each tag is attached to at least one other tag via alinker, a remote activating device that generates a magnetic fieldwithin a region of each tag, and a plurality of sensors configured todetect a signal from each tag while each tag is exposed to said magneticfield. In some embodiments, the tag is wireless and ideally minimallysized. In some embodiments, while powered, the tag generates its owntime varying magnetic field at one or more sideband frequencies. Theshape of the magnetic field is approximately that of a magnetic dipolepositioned at the tag. By monitoring the magnetic field at severalpositions with receiving antenna coils, also called sensors, sensingcoils, witness coils, or witness stations, the location of the tag isidentified. In some embodiments, the systems, devices, assemblies, andmethods further comprise an electrosurgical tool. In some embodiments,the electrosurgical tool, or a component attached to or in physicalproximity to the tool, comprises two or more location emitters that alsogenerate a magnetic field similar to a magnetic dipole. In someembodiments, the location emitters are driven with two differentfrequency signals that are also different from both the exciterfrequency and the tag response frequencies. In certain embodiments, thelocation emitters are wired to a signal supply source.

In some embodiments, a single exciter assembly is employed (e.g., asshown in FIG. 4A) to generate signals that interact with the tag and thelocation emitters in the attachment component associated with theelectrosurgical tool. In some embodiments, the exciter assembly iscontained in a single thin assembly. In some embodiments, the assemblycomprising the exciter further comprises sensors (e.g., the receivingantenna/sensing/witness station coils). In some embodiments, the exciterassembly is configured to be deployed under a patient that is undergoinga medical procedure. An exemplary procedure configuration is shown inFIG. 1 with patient 90 positioned on a surface 95 (e.g., mattress oroperating table). The surface 95 is held by a surface frame 97. Thepatient 90 has a lesion (e.g., tumor) 110 and an implanted tag 100positioned near, on, or in the tumor. An exciter assembly 250 ispositioned beneath the patient, and beneath the surface (e.g., on thesurface frame 97), and generates an electromagnetic field (not shown) ina region around the patient encompassing the position of the tag 100 anda medical device 20 (e.g., surgical device) in the operating field abovethe patient.

FIG. 2 shows an exemplary electrocautery surgical device (e.g., BOVIE)that finds use in some embodiments of the invention. The device 20includes a tip 25 providing an operating surface for treatment oftissues, two embedded location emitters 70 allows the system to sensethe location and position of the device 20, and a display unit 40 thatprovides visual information to a user (e.g., surgeon) about the locationof a tag in the patient.

In some embodiments, the exciter assembly is configured to provideenhanced detection of remote objects (e.g., tags and surgical devices)under a number of different settings that would otherwise complicatelocation, position, and distance assessment, particularly real-timeassessment of such factors.

In some embodiments, the systems and methods comprise a plurality ofcomponents. In some embodiments, a first component comprises at leasttwo linked tags (which may be used interchangeably with the term“marker”) whose location, position, distance, or other properties are tobe assessed. The linked tags described herein find use in a variety ofsystems and methods, such as those disclosed in WO2018031826A1,WO2017059228A1, WO2019236600A1, and WO2015112863A1, the entire contentsof each of which are incorporated herein by reference. In someembodiments, the systems and methods may comprise two linked tags, threelinked tags, four linked tags, five linked tags, or more than fivelinked tags. In some embodiments, the systems and methods comprise twolinked tags. For example, the systems and methods may comprise twolinked tags “A” and “B” that are attached to each other via a linker.Alternatively, the systems and methods may comprise three or more linkedtags. In such embodiments, the tags are linked in the sense that eachtag is attached to at least one other tag via the same or differentlinkers. For example, three tags may be linked, wherein tag “A” isattached to tag “B” via a linker and tag “B” is attached to tag “C” viaa linker. In some embodiments, at least one tag may be attached to twoor more tags. For example, three tags may be linked, wherein tag “A” isattached to tag “B” and tag “B” is attached to tag “C” and tag “C” isattached to tag “A”.

The tags are linked by a suitable linker. The linker may comprise anysuitable material that connects one tag to another. For example, thelinker may comprise plastic. Alternatively, the linker may comprise ashape-memory alloy. In some embodiments, the shape-memory alloy linkermay comprise any one or more metals selected from copper, iron,aluminum, nickel, titanium, manganese, silicon, zinc, or gold. Forexample, the shape-memory alloy may be a nickel-titanium alloy (e.g.Nitinol). As another example, the shape-memory alloy may be acopper-aluminum-nickel alloy. The metals in the shape-memory alloy maybe present in any suitable amount to achieve the desired alloycharacteristics. For example, for Nitinol, nickel and titanium aretypically present in atomic percentages ranging from 55%-60% nickel and40-45% titanium (by weight). For example, Nitinol 55 comprises 55%nickel and 45% Titanium. Alternatively, Nitinol 60 comprises 60% nickeland 40% titanium (wt %).

With reference to FIG. 15 , a first tag 500A and a second tag 500B arecoupled to a linker 504. The first tag 500A and the second tag 500B areglass tag that are mechanically coupled to the linker 504 by a heatshrink tubing 508 (or other similar means of retention). The linker 504is made of Nitinol wire and includes a torsion spring 512 positionedbetween the first tag 500A and the second tag 500B.

In some embodiments, the linker holds the two or more linked tags in afirst position prior to being placed within a subject, and the linkedtags subsequently form into a second position after being placed withinthe subject. For example, the linked tags may be held in a first,constrained arrangement prior to being placed within the subject suchthat the linked tags fit within the introduction device used to positionthe linked tags within the subject. This may be accomplished by the useof a plastic linker that folds or bends to allow the linked tags to fitwithin the introduction device. Alternatively, this may be accomplishedby using a shape-memory alloy linker, which may be chilled and molded toa first position to allow for placement within the introduction device.For example, the first position may comprise a linear shape, such thateach of the at least two tags are oriented in a straight line to fitwithin the introduction device (e.g. cannula). The linked tags maysubsequently enter into a second position after positioning within thesubject. For example, the shape-memory alloy (e.g. nitinol) linker couldre-fold to a remembered shape (e.g. L-shape, T-shape, V-shape, etc.)after positioning within the subject. As another example, the linker maybe plastic which is folded or bent to allow the linked tags to fitwithin the introduction device (e.g. cannula), and the plastic linkercould un-fold upon positioning within the subject to allow for thelinked devices to enter into a second position. Alternatively, ashape-memory alloy linker would be heated to the body temperature of thesubject upon positioning within the subject, thus allowing the alloy toreturn to its “remembered” shape.

The second position (e.g. the arrangement of the linked tags afterpositioning within the subject) maybe any suitable arrangement. Forexample, for embodiments with two linked tags the second position may bean L-shape, T-shape, V-shape, or X-shape. As another example, forembodiments with three or more linked tags the second arrangement may bea shape such as triangle, square, rectangle, etc. depending on thenumber of linked tags. Any of the above-described arrangements wouldallow for improved anchoring of the linked tags within the tissue of thesubject. In some embodiments, the linked tags are configured to beplaced in a subject at a surgical location or other clinically relevantlocation to mark a target region within a body.

In some embodiments, when in the second position, the tags are separatedby an angle within a range of approximately 15° to approximately 40°(i.e., the angle of tag separation). In some embodiments, the tags areseparated by approximately 30° in the second position for improved sixdegrees of freedom localization. In some embodiments, the tags areseparated by approximately 25° in the second position for improved sixdegrees of freedom localization. The tags are advantageously angledlarge enough with respect to each other to establish a full six degreesof freedom coordinate system, while also angled small enough withrespect to each other such that both tags can be powered at the sametime. A 0° angle between tags would not allow a full six degrees offreedom coordinate system to be established because the tag signal(s)would not vary as the tag is rotated about its long axis. Likewise, a90° angle between tags is not preferred because when one tag is fullyaligned to the exciter field and receiving full power, the other tagwill receive no power. The 90° angle between tags is also not preferredif one tag is pointed at the center of the other tag, because it isambiguous when the entire structure is flipped (i.e., a T has mirrorsymmetry, whereas a L does not).

In some embodiments, the second position may be achieved by the use ofone or more additional facilitating features (e.g. wires, lines, crimps,washers, etc.). For example, the at least two tags may be linked by ashape-memory alloy. The linker and/or tag(s) may be attached to a wireor a line, which may further comprise crimps, washers, etc. to ensurethat the at least two tags achieve the desired arrangement. For example,the wire or line may contain crimps and the spacing between crimps woulddetermine the angle at which the at least two tags are linked (e.g. theangle of the shape memory alloy linking the tags). In some embodiments,the first position of the at least two tags (e.g. the arrangement withinthe introduction device) may be a straight line, and the wire/line maybe pulled after placement of the device into the subject such that thecrimps apply the appropriate pressure on the linked tags/shape alloy,thus causing the alloy to bend in order to achieve the desired secondposition within the subject. In some embodiments, upon achieving thesecond position the wire/line may be cut and subsequently removed fromthe subject. Exemplary embodiments using these additional facilitatingfeatures are shown in FIG. 16 .

With reference to FIG. 16 , a first tag 600A and a second tag 600B aremechanically coupled to a linker 604. The first tag 600A and the secondtag 600B are glass tags that are retained by clips 608 cut and formedinto the linker 604. In the illustrated embodiment, the linker 604 iscut and formed Nitinol tubing with a bend 612 positioned between thefirst tag 600A and the second tag 600B. A wire 616 (or line) extendsbetween a first end 620 of the linker 604 and a second end 624 of thelinker 604. In the illustrated embodiment, the wire 616 passes throughbores formed in both the first and second ends 620, 624. Crimps 628A,628B are positioned along the wire 616 to create positional stops, and aself-cinching washer 632 is adjustably positioned along the wire 616.The self-cinching washer 632 is configured to slide along the wire 616to adjust the relative position the first end 620 along the wire 616with respect to the second end 624.

With reference to FIG. 17 , a first tag 700A and a second tag 700B aremechanically coupled to a linker 704. The first tag 700A and the secondtag 700B are retained to the linker 704 by corresponding clips 708formed on the linker 704. The linker 704 is a Nitinol linkage with abending portion 712 positioned between the first tag 700A and the secondtag 700B. In the illustrated embodiment, the linker 704 includes a grip716 at a first end 720 of the linker 704. In the illustrated embodiment,the grip 716 is a sphere configured to be graspable by a surgicalforceps, for example. As such, the tags 700A, 700B and the linker 704are easily manipulated by surgical tools or instruments.

With reference to FIG. 18 , the first tag 700A, the second tag 700B, andthe linker 704 are positioned within a packaging 724 (a sheath) for easydeployment into a bronchoscope, endoscope, or the like. The packaging724 is configured to fit into the scope working channel. Typically,scope working channels include discontinuities and the packaging 724prevents the linker 704 and tags 700A, 700B from becoming caught orstuck on those discontinuities. The packaging 724 is long enough toextend past features in the scope working channel, but short enough tonot extend where the working channel is bending into anatomy. In someembodiments, the packaging 724 includes a length within a range ofapproximately 100 cm to approximately 180 cm. The packaging 724surrounds the linker 704 (holding the linker 704 in a first position)except for the grip 716 is exposed. The grip 716 is graspable by asurgeon's forceps. In other words, the packaging 724 includes notch 728that exposes the grip 716. Once grasped, the forceps are used to pushthe tags 700A, 700B and linker 704 to a deployment site. Before reachingthe deployment site, the tags 700A, 700B and linker 704 are retrievableuntil released into position. As such, the linker 704 is retrievable ifdifficulties are encountered before the linker 704 is in position.

The use of at least two linked tags provides an advantage over only asingle tag in that fewer exciter field directions can be generated whilestill ensuring detection of at least one tag. Accordingly, the tags maybe placed within the subject at different orientations without riskingloss of detection of at least one of the two linked tags. In someembodiments, the linker is configured to hold the at least two tags in asecond position when present in tissue, wherein at least one of saidtags in said second position points approximately in the X dimension,and at least one of said tags points approximately in the Y dimension.In some embodiments, 3 tags are used, and in said second position: i)the first tag points approximately in the X dimension, ii) the secondtag points in approximately the Y dimension, and iii) and the third tagpoints in approximately in the Z dimension.

Any suitable spacing between each of the two or more linked tags may beused. For example, the two or more linked tags may be spaced from eachother at a suitable distance to allow the tags to mark a target region(e.g. a tumor) within the body. In such embodiments, the appropriatespacing between each of the at least two tags may be determined basedupon the estimated size and shape of the target (e.g. tumor). In someembodiments, the spacing between each of the linked tags is the same. Insome embodiments, the spacing between two or more of the linked tags isvariable (e.g. the distance between tag A and B may differ between thedistance between tag A and C, or the distance between tag B and C). Insome embodiments, the first tag and the second tag are separated by atleast approximately 2 mm to reduce cross-coupling affects.

In some embodiments, a second component comprises a remote activatingdevice (e.g., exciter assembly) that generates a magnetic field. In someembodiments, the second component is located in a device positioned near(e.g., below) a subject containing the linked tags. In some embodiments,a third component comprises a plurality of sensors (e.g. witnessstations) configured to receive a signal generated by the tags uponbeing exposed to the magnetic field generated by the second component.In some embodiments, the second and third components are physicallycontained in the same device (e.g., as shown in FIG. 4A). In someembodiments, a fourth component comprises a medical device locationemitter. The fourth component can be integrated into a medical device orattached or otherwise associated with an attachment component (e.g.,sheath). The fourth component comprises one or more location emitters(e.g., antennas that emit signals or other types of emitters) thatgenerate signals via electrical wire feeds or upon exposure to themagnetic field generated by the second component, said signalsdetectable by the third component. In some embodiments, a fifthcomponent comprises a computing device comprising a processor thatreceives information from the witness stations of the third componentand generates information about the relative locations, distances, orother characteristics of the tags, the medical device, and the witnessstations. In some embodiments, the fifth component comprises a displaythat displays such generated information to a user of the system.

In some embodiments, the first component is two or more tags (e.g., 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.). In some embodiments, the tagsare of identical type. In other embodiments, the tags are of differenttype.

Any number of tag designs may be employed. In some embodiments, at leastone of the linked tags comprises or consists of a ferrous pellet orparticle. When the ferrous object is introduced within a magnetic field,the object creates an irregularity in the alternating magnetic fieldwhich is detectable by sense coils contained within witness stations,producing a phase and amplitude shift from null. The null is restoredwhen the ferrous object is physically equidistant to two sense coils.

In some embodiments, at least one of the linked tags comprises aferrite-core coil antenna (e.g., resonant at 100-200 kHz) coupled to anintegrated circuit (IC), which is powered by an AC magnetic field atresonance. In some embodiments, the core is contained in an enclosure(e.g., a cylindrical glass or plastic housing). In some embodiments, theexciter antenna(s) is/are driven by a conventional oscillator and poweramplifier at a level sufficient to power the tag(s). In someembodiments, the implanted tag amplitude-modulate (AM's) the continuouswave (CW) carrier power from the exciter, thus emitting sidebands atfrequencies defined by a number programmed into the tag's counter. Insome embodiments, these sidebands, as well as the much stronger CWcarrier, are ultimately detected by the third component.

In some embodiments, at least one of the linked tags comprises aself-resonant object (e.g., a small ferrite core with a wound inductor).The wound inductor possesses inter-winding capacitance that incombination with the inductance produces a high frequency resonantcircuit. In some embodiments, at least one of the linked tags comprisesa resonant object (e.g., the self-resonant object is equipped with achip capacitor to produce resonance at a prescribed frequency). Incertain embodiments, the chip capacitor is not a dielectric resonantantenna, and instead is a standard thin film capacitor, or a multi-layerceramic capacitor (MLCC). Dielectric resonant antenna capacitors may notbe well suited for use in the present methods, as dielectric resonantantenna capacitors are less effective at low frequencies (e.g. 100-200kHz). In contrast, standard thin film capacitors or MLCCs may be createdto have consistent functionality at low frequencies (e.g. 100-200 kHz).Moreover, standard thin film capacitors or MLCCs may be manufactured toprovide consistent functionality independent of temperature, such thatthey will work effectively both at ambient temperature and at bodytemperature (e.g. once placed within a subject). In addition, standardthin film capacitors or MLCCs are less expensive than dielectricresonant antennas.

In some embodiments, the tag(s) comprise a resonant or self-resonantobject with a diode. A diode in combination with an LC circuit producesa sub-harmonic frequency when immersed in a magnetic field of sufficientstrength (imposed voltage exceeds the diode's band-gap potential). Insome embodiments, the tag(s) comprise a resonant object or self-resonantobject with an active modulator (e.g., integrated circuit amplitudemodulates resonant circuit). In some embodiments, detection occurssimilar to a full duplex (FDX) radio frequency identification (RFID)except that the modulation pattern is a simple sub-harmonic rather thana coded binary pattern; in some embodiments, the detection occurs afterexcitation similar to a half-duplex (HDX) mode of operation.

In some embodiments, at least one of the linked tags are configured forsingle-use. In some such embodiments, the linked tag(s) can be disabledor deactivated (e.g., like an EAS tag). This is particularly usefulwhere multiple tags are used in a procedure where individual tags areturned off to make detection of other tags easier (e.g., to avoid orreduce interference between multiple tags). In some embodiments, a burstof energy from an external device is used to disable or deactivate atag. In other embodiments, at least one of the linked tags has aninternal control component that, upon receiving instruction from anexternal device, turns the tag on or off (e.g., the tag stops “talking”temporarily or permanently).

In some embodiments, each of the linked tags has an exterior length,width, and depth, wherein the length is 30 mm or less (e.g., 20 mm orless, . . . , 10 mm or less, . . . , 9 mm or less, . . . , 8 mm or less,. . . , 5 mm or less, . . . , 3 mm or less, . . . , etc.), the width is5 mm or less (e.g., 4 mm or less, . . . , 3 mm or less, . . . , 2 mm orless, . . . 1 mm or less, . . . 0.5 mm or less, . . . , etc.), and thedepth is 5 mm or less (e.g., 4 mm or less, . . . , 3 mm or less, . . . ,2 mm or less, . . . 1 mm or less, . . . 0.5 mm or less, . . . , etc.).

In some embodiments, each of the linked tags is contained in a housingor sheath. In some embodiments, no housing is employed. In someembodiments, at least one of the linked tags is contained in a housingand at least one of the linked tags is not contained in a housing. Insome embodiments, the housing comprises a biocompatible material. Insome embodiments, the housing provides a liquid and/or gas resistantbarrier separating the signal source from the exterior of the housing.In some embodiments, the housing is small, permitting administration ofthe linked tags through a needle, cannula, endoscope, catheter, or othermedical device. In some such embodiments, the housing has an exteriorlength, width, and depth, wherein the length is 30 mm or less (e.g., 20mm or less, . . . , 10 mm or less, . . . , 9 mm or less, . . . , 8 mm orless, . . . , 5 mm or less, . . . , 3 mm or less, . . . , etc.), thewidth is 5 mm or less (e.g., 4 mm or less, . . . , 3 mm or less, . . . ,2 mm or less, . . . 1 mm or less, . . . 0.5 mm or less, . . . , etc.),and the depth is 5 mm or less (e.g., 4 mm or less, . . . , 3 mm or less,. . . , 2 mm or less, . . . 1 mm or less, . . . 0.5 mm or less, . . . ,etc.). The housing can be of any desired shape. In some embodiments, thehousing is cylindrical along the length axis. In some embodiments, thehousing is shaped like a grain of rice (e.g., cylindrical with roundedends). In some embodiments, the housing is shaped like a pillar (e.g.,cylindrical with flat ends). In some embodiments, the housing ispolygonal along the length axis (e.g., triangular, square, rectangular,trapezoidal, pentagonal, etc., in cross-section). In some embodimentsthe housing has struts or other fasteners to keep the tag in place,avoiding migration in tissue. These struts may deploy upon placement intissue. In some embodiments the fastener may be a biocompatible materialthat bonds with surrounding tissue. Advantageously, embodiments of thetwo linked tags that do not include a sheath are able to be positionedwith a tighter bend radius.

In some embodiments, the housing is a single uniform componentsynthesized around the interior components of the tag. In otherembodiments, the housing is made of two or more separate segments thatare sealed together after introduction of the interior components of thetag. In some embodiments, the tag is completely or partially covered ina coating. In some embodiments, the coating comprises a biocompatiblematerial (e.g., parylene-C, etc.).

In some embodiments, one or more of the linked tags does not compriseany power source. In some embodiments, each of the linked tags do notcomprise any power source.

For example, in some embodiments, the signal is generated from thesignal source in response to a magnetic field as the activation event(i.e., electromagnetic induction).

In some embodiments, at least one of the linked tags comprise aradio-frequency identification (RFID) chip (e.g., in a housing). Forexample, each of the linked tags may comprise an RFID chip. In someembodiments, the RFID chip comprises a radio-frequency electromagneticfield coil that modulates an external magnetic field to transfer a codedidentification number and/or other coded information when queried by areader device. In some embodiments, the RFID chip collects energy froman EM field generated by the second component (or other device) and thenacts as a passive transponder to emit microwaves or UHF radio waves. Insome embodiments, the RFID chip is read-only. In other embodiments, itis read/write. The technology is not limited by the nature of theinformation provided by the RFID chip. In some embodiments, theinformation includes a serial number, lot or batch number, timeinformation (e.g., production date; surgery date; etc.);patient-specific information (e.g., name, family history, drugs taken,allergies, risk factors, procedure type, gender, age, etc.);procedure-specific information; etc. The technology is not limited bythe frequency used. In some embodiments, the RFID frequency is in the120-150 kHz band (e.g., 134 kHz), the 13.56 MHz band, the 433 MHz band,the 865-868 MHz band, the 902-928 MHz band, the 2450-5800 MHz band, orthe like. In some embodiments, the RFID chip is incorporated withbrowser-based software to increase its efficacy. In some embodiments,this software allows for different groups or specific hospital staff,nurses, and patients to see real-time data relevant to the tag,procedure, or personnel. In some embodiments, real-time data is storedand archived to make use of historical reporting functionality and toprove compliance with various industry regulations. In some embodiments,the RFID chip reports sensor data (e.g., temperature, movement, etc.).In some embodiments, the RFID chip contains or collects information thatis read at a later time (e.g., after surgery). In some embodiments,information is reviewed during surgery. For example, a message may beprovided to the surgeon (e.g., “the chip is just to the left of thetumor”) to assist in guiding the surgeon (e.g., optimizing removal of atumor with the appropriate margins).

In some embodiments, each of the two or more linked tags is composed ofthe same components. In other words, each of the linked tags does notneed to be composed of components with different electrical propertiesin order for the tags to be uniquely identifiable. In some embodiments,each of the linked tags consists of or consists essentially of thesignal source and the housing or the signal source, the housing, and theRFID chip. In some embodiments, the tag (e.g., via the chip) emits anultrasound signal (e.g., gray scale, spectral, or color Doppler) suchthat the signal is detectable by an ultrasound probe or a hand-heldDoppler unit.

In some embodiments, a tag is heated during a procedure (e.g., viaexposure to an external energy source). In some such embodiments,heating may be used to assist in coagulation or precoagulation of tissueor to provide thermotherapy (see e.g., U.S. Pat. Publ. No. 2008/0213382,herein incorporated by reference in its entirety). Heating may also beused to improve the efficacy of radiation therapy.

In some embodiments, the second component provides a remote activatingdevice. In some embodiments, the remote activating device comprises atleast one excitation coil. In some embodiments, the remote activatingdevice comprises two or more excitation coils (e.g., exciter assemblyshown in FIG. 4A). In some embodiments, the at least one excitation coilis provided on a base substrate. The base substrate may be composed ofany suitable material, which may be, for example, polycarbonate or thelike and is typically nonmagnetic and non-electrically conducting.

In some embodiments, the excitation coils are provided in a patch or padthat is placed on the patient or on the operating table, although it canbe positioned in any desired location within functional distance of thetags. In some embodiments, the remote activating device provides an ACmagnetic field originating from one or more exciter antennas. In someembodiments, where the system is used to locate breast tumors, the patchencircles the treated breast or is placed otherwise near the breast.Similar approaches may be used for other targeted areas of a body. Insome embodiments, a pad containing the excitation coil(s) are placedbeneath the patient. In such embodiments, a large coil or multiple coilsare employed. The excitation coil(s) may comprise or consist of severalturns of a flat conductor patterned on a dielectric substrate, or maycomprise or consist of magnet wire wound around a suitable mandrel; thecoil is powered by an external frequency source, and the magnetic fieldemanating from the coil penetrates the patient's body to excite thetags, whose emissions are detected by a detection component.

In some embodiments, the excitation coil or coils are contained in abelt that is placed around the subject or a portion of the subject. Insome embodiments, the external excitation coil may further be used forother aspects of the patient care, such as for radiotherapy or to act asa ground current return pad used in electrosurgery. In some embodiments,the remote activating device emits light (e.g., laser light). In someembodiments, the remote activating device is configured for single use(e.g., is disposable).

In some embodiments, the remote activating device employs an unmodulatedconstant frequency activation (i.e., the activation signal has constantamplitude and frequency). In some embodiments, the remote activatingdevice employs an unmodulated swept frequency (i.e., the activationsignal has constant amplitude and swept frequency between twoendpoints). Such devices find use with resonant-type tags such that adetectable change in the activation signal's amplitude occurs when thetransmitted frequency coincides with the tag's resonant frequency. Insome embodiments, the remote activating device employs a pulsedfrequency (i.e., the activation signal comprises brief excitation pulsesat a periodic frequency, which may be comprised of two closely-relatedfrequencies whose sum or difference is the response frequency of thetag). The pulsed activation produces a post-pulse sinusoidal decaysignal. A tag alters the characteristic of the decaying signal, eitherin amplitude or time.

The system provided herein is advantageous in that each of the at leasttwo linked tags may respond to a single transmitted frequency (e.g.activation signal), such as the activation signal provided by the remoteactivating device. In other words, the transmitted frequency is commonto all tags. For example, each of the at least two linked tags may beprogrammed to generate a unique frequency in response to the singletransmitted frequency provided by the activation device. The at leasttwo linked tags may be programmed to respond to a broad range offrequencies (e.g. 100-150 kHz), with the response frequency of each tagscaling according to the stimulating frequency.

In some embodiments, the remote activating device comprises a hand-heldcomponent. In some embodiments, the hand-held component is lightweightto allow a surgeon to hold and manipulate the component over the courseof a procedure (e.g., 5 kg or less, 4 kg or less, 3 kg or less, 2 kg orless, 1 kg or less, 0.5 kg or less, 0.25 kg or less, or any rangetherein between, e.g., 0.5 to 5 kg, 1 to 4 kg, etc.). In someembodiments, the hand-held component is shaped like a wand, having aproximal end that is held by the physician and a distal end that ispointed towards the treated subject or tissue harboring the linked tags.In some embodiments, the hand-held component is shaped like an otoscope,having a distal end that terminates at an angle (e.g., right angle) fromthe body of the component. In some embodiments, the remote activatingdevice comprises an antenna that generates a magnetic field. In someembodiments, the remote activating device has only a single antenna(i.e., is monostatic). In some embodiments, the remote activating devicehas only two antennas (i.e., is bistatic).

In some embodiments, the magnetic field of the remote activating device(e.g., exciter assembly shown in FIG. 4A) is controlled by a processorrunning a computer program. In some embodiments, the remote activatingdevice comprises a display or user interface that allows the user tocontrol the remote activating device and/or monitor its functions whilein use. In some embodiments, the remote activating device provides avisual, audio, numerical, symbol (e.g., arrows), textual, or otheroutput that assists the user in locating the linked tags or identifyingthe distance to or direction of the tags from the remote activatingdevice.

In some embodiments, the plurality of witness coils of the thirdcomponent collectively provide several antennas (e.g. witness antennas)at multiple defined locations relative to the tags and configured toreceive a signal generated by one or more tags upon being exposed to themagnetic field generated by the second component.

In some embodiments, each witness coil feeds a receiver channel, whichis time-division multiplexed (TDM′d) to reduce the receiver complexity.Fixed witness stations of defined locations relative to the tag(s) andeach other (e.g., arrayed along the patient) contain one or more (e.g.,one to three) witness coils arranged in a locally orthogonal manner tosense various components of the AC magnetic field from the tag(s). Insome embodiments, one or more or all of these witness coils in thewitness stations is also TDM′d into a receiver channel, reducingcomplexity, as well as cross-talk between antennas.

In some embodiments, witness coils comprise or consist of aferrite-loaded cylindrical coil antenna (e.g., witness antenna), tuned(e.g., with one or more capacitors in parallel) for resonance at thefrequency of an exciter (e.g., tag or emitter), (e.g., 100-200 kHz).Typical dimensions of a witness coils are 3-5 mm diameter and 8-12 mmlength, although both smaller and larger dimensions may be employed. Insome embodiments, witness station antenna has a ferrite core size of0.25×1 inch and contains 75-80 turns of a 10/46 (10 strands of #46) Litzwire which provides 0.157 mH (Q=53) (75 Turns).

In some embodiments, each witness coil is symmetrically wound about aferrite core and connected to the secondary of a small balun transformerthrough two series capacitances, one for each wire from the coil. Thetotal series capacitance is selected to resonate with the inductance ofthe coil, and the turns ratio of the balun transformer may be chosen tomatch the real impedance of the resonant coil/capacitor circuit to thetransmission line, typically 50 Ohms. The real impedance of the resonantcoil/capacitor circuit is typically 10 to 25 Ohms but may vary from justa couple Ohms to greater than 50 Ohms and may be adequately matched byappropriate choice of balun transformer primary and secondary turns. Inaddition to its role as impedance transformer, the balun minimizes anyelectric field generation/susceptibility from the witness coil assembly;alternately, it may be thought of as removing common mode effects.

In some embodiments, each witness station contains 1-3 witness antennasoriented orthogonally to each other and further arranged to have minimumcross-talk (i.e., interference with one another). The component housingthe witness stations further comprises one or more receiver channels forcollecting information obtained by the antennas of the witness stations.In some embodiments, the receiver comprises or consists of one or morechannels, each channel fed by one or more (via a multiplexing switch)witness antennas.

In some embodiments, the witness stations are provided below the patient(e.g., in a pad, garment, or other device positioned below the patient).In some embodiments, the witness stations are integrated into a surgicaltable or imaging device in which a patient is placed during a medicalprocedure. In some embodiments, the witness stations are placed on thefloor, wall, or ceiling of the operating room or in a medical transportvehicle. In some embodiments, the witness stations are integrated intoor attached to a medical device used in the medical procedure.

In some embodiments, a fourth component provides a medical devicelocation emitter in an attachment component (see FIGS. 9-12 ) to allowthe system to determine the location, position, distance, or othercharacteristic of a medical device relative to the tag or tags. In someembodiments, the medical device location emitter or emitters areintegrated into a medical device or into an attachment component. Inother embodiments, they are attachable to a medical device. In some suchembodiments, the location emitters are provided in an attachmentcomponent (e.g., sleeve) that slips over a portion of a medical device.The location emitters may operate as and/or comprise the same materialsas the tags, but are positioned on or near a medical device rather thanwithin tissue. For example, in some embodiments, the emitters comprisecoils that are excited with both carrier and/or sidebands, enabling theemitters to emit signals as though it were a tag. In other embodiments,the location emitters are wired to a power and signal source.

In some embodiments, location of the location emitters is accomplishedgeometrically by measuring the quasi-simultaneous power detected fromthe emitters at a plurality of witness stations (e.g., four or morestations), and using the power differences to perform vector math thatdetermines the location of the emitter without ambiguity. This processis facilitated by a preliminary calibration using a known tag in a knownlocation prior to the procedure.

In some embodiments, the component (e.g., attachment component) thatcontains the location emitters may further comprise a display to assistthe user in directing the medical device to the linked tags during asurgical procedure. In some such embodiments, a visual or audio displayis provided on or associated with the medical device that receiveslocation information about one or more of the linked tags from thecomputer system. The display may be one or more directional indicatorssuch as LEDs, that indicate direction and/or distance to the tag(s).Color changes may be employed to indicate “on target” versus “offtarget” positions. In certain embodiments, the display comprises a firstdisplay for presenting distance to tag information (e.g., visual,audible, lights, color, vibration, tactile, etc.); a second display forpresenting vertical axis orientation, such as a preset preferred anglefor approaching the linked tags in a patient (e.g., a visual, audible,lights, colors, vibration, tactile, etc. display); and/or a thirddisplay for presenting horizontal orientation (e.g., left to rightinformation so the surgical device can be centered when approaching thetags). In some embodiments, the display comprises a plurality ofdisplays (e.g., visual, audible, sensory, etc.) that allow the correctpitch and yaw axes to be employed (to minimize non-target tissuedamage), and/or further a display that provides distance to taginformation. In certain embodiments, a series of lights and/or soundsare provided on the display that guide the surgeon (e.g., the surgeonattempts to keep the lights in a center of an “X” series of lights,and/or to keep the volume of warning sounds off or as low as possible).

Vectors describing the location of the location emitters are used toprovide visualization guidance to the surgeon about the spatialrelationship of a medical device (e.g., particularly its tip) to animplanted tag, or (e.g., with computational guidance) to a lesionboundary. Use of multiple location emitters on an attachment componentattached to a medical device provides vectors to determine the device'sprincipal axis using the same vector math. Where a more complex medicaldevice, such as a robotic surgical system (e.g., da Vinci surgicalsystem) is employed, multiple location emitters located on multipledifferent locations of the device are employed to provide location,orientation, and other position information of multiple components(e.g., arms) of the device. In some embodiments, the location emittersare also used as detectors (e.g., provide witness stations on themedical device).

In some embodiments, a fifth component provides one or more computingsystems comprising one or more computer processors and appropriatesoftware to analyze, calculate, and display tag and emitter positioninformation (see, part 210 in FIG. 4A). In some embodiments, the displayprovides a graphical representation of the tag(s), patient, and/ormedical device on a monitor. In other embodiments, the display providesdirectional information for moving or positioning the medical device. Insome embodiments, the system automatically (e.g., robotically) controlsthe medical device or one or more functions thereof. In someembodiments, the display integrates tag and/or medical deviceinformation with previously obtained or concurrently obtained medicalimages of the patient or target tissue (e.g., CT, MRI, ultrasound, orother imaging modalities). For example, in some embodiments, an imageindicating a tag or tags is fused with an image of the subject's tissueor body region obtained from an imaging device. In some embodiments,information is analyzed in real-time. In some embodiments, informationis analyzed at one or more discrete time points.

In some embodiments, the fifth component provides command and controlfunctions for a user of the system. In some embodiments, the fifthcomponent has information stored thereon that helps guide theinformation displayed on the attachment component. For example, theinformation may include data on the type of medical device theattachment component is attached to, or what tip or cutting implement isbeing used with a particular medical device. In this regard, the preciselocation of the cutting tip of a medical device and its relation to thetag(s) (e.g., distance to the tag(s)) is communicated to the surgeon(e.g., for very precise instructions on cutting tissue). Suchinformation is, for example in some embodiments, manually entered into acontrol unit or attachment component by the user, or automatically found(e.g., by a barcode or other indicator) when a detection component isattached to a particular medical device.

The system finds use with a wide variety of medical devices andprocedures. In some embodiments, the surgical device comprises anelectrical surgical device that is turned on and off by a user, whereina control unit that is part of the fifth component allows the remoteactivating device to generate the magnetic field when the electricalsurgical device is off, and prevents the remote activating device fromgenerating the magnetic field when the electrical surgical device is on(e.g., ensuring that the surgical device and detection system do notinterfere with one another). In other embodiments, the surgical devicecomprises a power cord, wherein an AC current clamp is attached to thepower cord, wherein the AC current clamp is electrically-linked orwirelessly linked to the control unit, wherein the AC current clampsenses when the electrical surgical device is on or off and reports thisto the control unit (e.g., such that the control unit can ensure thatthe magnetic field from the surgical device and from the remoteactivating device are not active at the same time).

In certain embodiments, the surgical device comprises an electrocauterydevice, a laser cutting device, a plasma cutting device, or a metalcutting device (e.g., a surgical device manufactured by BOVIE MEDICAL).Additional examples of medical devices that find use in embodiments ofthe system are found, for example, in the following U.S. Pat. Nos.9,144,453; 9,095,333; 9,060,765; 8,998,899; 8,979,834; 8,802,022;8,795,272; 8,795,265; 8,728,076; 8,696,663; 8,647,342; 8,628,524;8,409,190; 8,377,388; 8,226,640; 8,114,181; 8,100,897; 8,057,468;8,012,154; 7,993,335; 7,871,423; 7,632,270; 6,361,532; all of which areherein incorporated by reference in their entireties, and particularlywith respect to the hand-held medical devices disclosed therein.

In some embodiments, the attachment component has thereon, or attachedthereto, a display component for directing the surgeon to the tag ortags. In some embodiments, the display component provides: i) a spatialorientation indicator (e.g., visual, audible, etc.), and/or ii) adistance-to-tag indicator (e.g., visual, audible, etc.). In someembodiments, the display component comprises a first display forpresenting distance to tag information (e.g., visual, audible, lights,color, vibration, tactile, etc.), a second display for presentingvertical axis orientation, such as a preset preferred angle forapproaching a tag in a patient (e.g., a visual, audible, lights, colors,vibration, tactile, etc. display); and/or a third display for presentinghorizontal orientation (e.g., left to right information so the surgicaldevice can be centered when approaching the tag). In some embodiments,the display component comprises a plurality of displays (e.g., visual,audible, sensory, etc.) that allow the correct pitch and yaw axes to beemployed (to minimize non-target tissue damage), and/or further adisplay that provides distance to tag information. In certainembodiments, the medical device is moved around the patient's body priorto surgery to orient the emitters and the display component. In certainembodiments, a series of lights and/or sounds is provided on the displaycomponent that guides the surgeon (e.g., the surgeon attempts to keepthe lights in a center of an “X” series of lights, and/or to keep thevolume of warning sounds off or as low as possible).

The linked tags disclosed herein are not limited to placement within aparticular body region, body part, organ, or tissue. For example, insome embodiments, the tags are placed in the cephalic, cervical,thoracic, abdominal, pelvic, upper extremities, or lower extremitiesregion of the body. In some embodiments, the tags are placed within anorgan system, such as the skeletal system, muscular system,cardiovascular system, digestive system, endocrine system, integumentarysystem, urinary system, lymphatic system, immune system, respiratorysystem, nervous system or reproductive system. In some embodiments, thetags are placed within an organ. Such organs may include the heart,lungs, blood vessels, ligaments, tendons, salivary glands, esophagus,stomach, liver, gallbladder, pancreas, intestines, rectum, anus,hypothalamus, pituitary gland, pineal gland, thyroid, parathyroid,adrenal glands, skin, hair, fat, nails, kidneys, ureters, bladder,urethra, pharynx, larynx, bronchi, diaphragm, brain, spinal cord,peripheral nervous system, ovaries, fallopian tubes, uterus, vagina,mammary glands, testes, vas deferens, seminal vesicles, and prostate. Insome embodiments, the tags are placed within tissues, such asconnective, muscle, nervous, and epithelial tissues. Such tissues mayinclude cardiac muscle tissue, skeletal muscle tissue, smooth muscletissue, loose connective tissue, dense connective tissue, reticularconnective tissue, adipose tissue, cartilage, bone, blood, fibrousconnective tissue, elastic connective tissue, lymphoid connectivetissue, areolar connective tissue, simple squamous epithelium, simplecuboidal epithelium, simple columnar epithelium, stratified epithelium,pseudostratified epithelium, and transitional epithelium.

In some embodiments, the tissue region where the tags are locatedcomprises a lesion. In some embodiments, the lesion is a tumor or atissue region identified as being at risk for forming a tumor. Forexample, one tag may be placed at a boundary of a tumor and another tagmay be placed at a second boundary of a tumor, such that the linked tagsdelineate the outer edges of the tumor. In some embodiments, the lesionis fibrotic tissue. In some embodiments, the lesion is an inflamed orinfected region. In some embodiments, the tags are placed within a lumento detect function or other process of the organ or provide localizinginformation. For example, the tags could be swallowed, or placed into ahollow organ via endoscopy. In some embodiments, the tissue region ishealthy tissue. In some embodiments, the two linked tags are positionedoffset from a lesion. In some embodiments, the two linked tags arepositioned within an airway up to approximately 5 mm.

In some embodiments, the linked tags are placed within a solid tumor.Examples of solid tumors into which the tags may be placed includecarcinomas, lymphomas, and sarcomas, including, but not limited to,aberrant basal-cell carcinoma, acinar cell neoplasms, acinic cellcarcinoma, adenocarcinoma, adenoid cystic carcinoma,adenoid/pseudoglandular squamous cell carcinoma, adnexal neoplasms,adrenocortical adenoma, adrenocortical carcinoma, apudoma, basal cellcarcinoma, basaloid squamous cell carcinoma, carcinoid,cholangiocarcinoma, cicatricial basal-cell carcinoma, clear celladenocarcinoma, clear cell squamous-cell carcinoma, combined small cellcarcinoma, comedocarcinoma, complex epithelial carcinoma, cylindroma,cystadenocarcinoma, cystadenoma, cystic basal-cell carcinoma, cysticneoplasms, ductal carcinoma, endometrioid tumor, epithelial neoplasms,extramammary Paget's disease, familial adenomatous polyposis,fibroepithelioma of Pinkus, gastrinoma, glucagonoma, Grawitz tumor,hepatocellular adenoma, hepatocellular carcinoma, hidrocystoma, Hurthlecell, infiltrative basal-cell carcinoma, insulinoma, intraepidermalsquamous cell carcinoma, invasive lobular carcinoma, inverted papilloma,keratoacanthoma, Klatskin tumor, Krukenberg tumor, large cellkeratinizing squamous cell carcinoma, large cell nonkeratinizingsquamous cell carcinoma, linitis plastica, liposarcoma, lobularcarcinoma, lymphoepithelial carcinoma, mammary ductal carcinoma,medullary carcinoma, medullary carcinoma of the breast, medullarythyroid cancer, micronodular basal-cell carcinoma, morpheaformbasal-cell carcinoma, morphoeic basal-cell carcinoma, mucinouscarcinoma, mucinous cystadenocarcinoma, mucinous cystadenoma,mucoepidermoid carcinoma, multiple endocrine neoplasia, neuroendocrinetumor, nodular basal-cell carcinoma, oncocytoma, osteosarcoma, ovarianserous cystadenoma, Paget's disease of the breast, pancreatic ductalcarcinoma, pancreatic serous cystadenoma, papillary carcinoma, papillaryhidradenoma, papillary serous cystadenocarcinoma, papillary squamouscell carcinoma, pigmented basal-cell carcinoma, polypoid basal-cellcarcinoma, pore-like basal-cell carcinoma, prolactinoma, pseudomyxomaperitonei, renal cell carcinoma, renal oncocytoma, rodent ulcer, serouscarcinoma, serous cystadenocarcinoma, signet ring cell carcinoma,signet-ring-cell squamous-cell carcinoma, skin appendage neoplasms,small cell carcinoma, small cell keratinizing squamous cell carcinoma,somatostatinoma, spindle cell squamous cell carcinoma, squamous cellcarcinoma, squamous cell lung carcinoma, squamous cell thyroidcarcinoma, superficial basal-cell carcinoma, superficial multicentricbasal-cell carcinoma, syringocystadenoma papilliferum, syringoma,thymoma, transitional cell carcinoma, verrucous carcinoma, verrucoussquamous cell carcinoma, VlPoma, and Warthin's tumor.

In some embodiments, placing the linked tags comprises the steps ofinserting an introduction device into the subject and introducing thelinked tags through the introduction device into the subject. In someembodiments, the introduction device is a needle, cannula, or endoscope.In some embodiments, the linked tags are forced through the introductiondevice (e.g., via physical force, pressure, or any other suitabletechnique) and released into the subject at the distal end of theintroduction device. After the tags are placed, the introduction deviceis withdrawn, leaving the tags at the desired location with the subject.In some embodiments, the introduction of the tags is guided by imagingtechnology. In some embodiments, the linked tags are positioned within apackaging while being moved into the desired position.

In the embodiments provided herein, multiple tags are placed into thesubject. The tags are linked together (e.g. by a linker). The tags maybe of identical type or may differ (e.g., differ in signal type). Thetags may be placed in proximity to one another or at distant locations.Multiple tags are used, in some embodiments, to triangulate the locationintended for medical intervention.

In some embodiments, the tags are further used as fiducials forradiotherapy (or other targeted therapy). The location of the tags isidentified with an external reader and used to place, for example, laserlight on the skin surface exactly where the chip is located. Thiseliminates the need to use X-ray, CT, or fluoroscopy to see thefiducials. This also decreases or eliminates the need to put skinmarkers (e.g., tattoos) on patients. This also helps in respiratorycompensation as the fiducial moves up and down with a tumor in the lungor abdomen. Therefore, one can conduct real-time radiation only when thetumor is in the correct position and decrease damage to the backgroundtissue (e.g., avoid burning a vertical stripe in the patient as thetumor moves up and down). The use as fiducials for director therapy(e.g., radiation therapy) also enhances triangulation as depthinformation (based on signal strength) assists in localization of thetumor to minimize collateral damage.

In some embodiments, provided herein are systems and methods employingone or more or all of: a) two or more linked tags (e.g., comprising anantenna; e.g., a coil antenna; e.g., a ferrite-core coil antenna; e.g.,that resonates at 100-200 kHz; e.g., coupled to an integrated circuit);b) a remote activating device that generates a magnetic field within aregion of the tag; and c) a plurality of sensors (e.g. witnessstations), each of the witness stations comprising an antenna configuredto detect information generated by the tags or a change in a magneticfield generated by the remote activating device caused by said tags. Insome embodiments, at least one of the linked tags emits sidebands atdefined frequencies upon activation by a magnetic field and the witnessstations detect such sidebands. In some embodiments, at least one of thelinked tags emits the sidebands at frequencies defined by a numberprogrammed into a counter in the tag(s).

In some embodiments, the remote activating device comprises anexcitation coil that is, for example, powered by a generatorelectrically connected to the remote activating device. In someembodiments, the remote activating device comprises a pad configured tobe placed in proximity to (e.g., under, above, beside) a patient havingthe linked tags embedded in the patient. In some embodiments, the padalso contains the witness stations.

In particular embodiments, provided herein are devices and systemscomprising: a remote activating device that generates a magnetic fluxwithin a region of a tag, wherein the remote activating devicecomprises: a) a base substrate, b) at least one exciter coil attached tothe base substrate that generates the magnetic flux, and c) a pluralityof witness station assemblies attached to the base substrate, whereineach of the witness station assemblies comprises a witness coil having asensing axis and comprising: i) a core having a coil-free proximal end,a coil-free distal end, and a central region, wherein the core comprisesmetal, and ii) coil windings wound around the central region of thecore, wherein each of the witness station assemblies is oriented on thebase substrate such that the sensing axis of each of the witness coils:A) runs from the proximal end to the distal end of the core, and B) isorthogonal to, or substantially orthogonal to: i) the magnetic flux,and/or ii) the at least one exciter coil. In particular embodiments, theat least one exciter coil is configured to selectively flow current in aclockwise or counterclockwise direction. In other embodiments, thesensing axis of each of the witness coils is substantially orthogonal tothe magnetic flux for both the clockwise, and the counterclockwise,directions.

In certain embodiments, each of the exciter coils comprises a centralplane, and wherein each of the witness station assemblies is furtheroriented on the base substrate such that the sensing axis of each of thewitness coils: C) is co-planar with the central plane of each of theexciter coils. In particular embodiments, the magnetic flux does notinduce a signal in the witness coils when generated in substantially theX and/or Y directions.

In other embodiments, each of the witness station assemblies furthercomprises: i) first and second witness coil brackets, and ii) first andsecond elastomeric parts, and wherein the coil-free proximal end of thecore is secured between the first witness coil bracket and the firstelastomeric part, and wherein the coil-free distal end of the core issecured between the second witness coil bracket and the secondelastomeric part. In further embodiments, the first and second witnesscoil brackets each comprises at least one adjustment part. In otherembodiments, the at least one adjustment part comprises at least onescrew and/or at least one rod. In particular embodiments, providedherein are methods of employing the adjustment parts to adjust thewitness coils such that their sensing axes are orthogonal to, orsubstantially orthogonal to the magnetic flux, and/or the at least oneexciter coils.

In some embodiments, the at least one adjustment part allows the sensingaxis of each of the witness coils to be adjusted such that it isorthogonal to, or substantially orthogonal to, the magnetic flux in oneor more of the X, Y, or Z directions. In some embodiments, the sensingaxis of each of the witness coils may be adjusted such that it isorthogonal to the X and Y directions. In further embodiments, themagnetic flux may be further selectively generated in substantially theZ direction, and wherein each of the witness station assemblies isoriented on the base substrate such that the sensing axis of each of thewitness coils is orthogonal to, or substantially orthogonal to, themagnetic flux the Z direction. In further embodiments, the magnetic fluxdoes not induce a signal in the witness coils when generated insubstantially the Z direction. In further embodiments, the at least oneadjustment part allows the sensing axis of each of the witness coils tobe adjusted such that it is orthogonal to, or substantially orthogonalto, the magnetic flux in each of the X, Y, and Z directions. In someembodiments, the metal comprises ferrite.

In other embodiments, each of the witness station assemblies is orientedon the base substrate such that the sensing axis of each of the witnesscoils is orthogonal to, or substantially orthogonal to the at least oneexciter coil. For example, each of the witness station assemblies may beoriented on the base substrate such that the sensing axis is orthogonalto, or substantially orthogonal to, the at least two exciter coils, theat least three exciter coils, or the at least four exciter coils. Insome embodiments, each of the witness station assemblies is oriented onthe base substrate such that the sensing axis of each of the witnesscoils is orthogonal to, or substantially orthogonal to the magnetic fluxin each of the X and Y directions. In further embodiments, the four ormore exciter coils is four exciter coils or six exciter coils. In otherembodiments, the four exciter coils are in a layout of two rows centeredat coordinates (X1, Y1), (X1, Y2), (X2, Y1), and (X2, Y2). In additionalembodiments, the remote activating device comprises three current flowconfigurations: a) all current clockwise to simulate an exciter coilaligned, or substantially aligned, with a plane normal to the Z axis; b)exciter coils centered at (X2, Y1), (X2, Y2) running currentcounter-clockwise to simulate an exciter coil aligned, or substantiallyaligned, to the X axis; and c) exciter coils centered at (X1, Y2), (X2,Y2) running current counter-clockwise to simulate an exciter coilaligned, or substantially aligned, to the Y axis.

In some embodiments, the sensing axis of the witness coil issubstantially orthogonal when isolation between the at least fourexciter coils and the witness coil is 60 dB or greater in the X and Ydirections. In other embodiments, the sensing axis of the witness coilis substantially orthogonal when isolation between the at least fourexciter coils and the witness coil is 60 dB or greater in the X, Y, andZ directions.

In certain embodiments, provided herein are systems and devicescomprising: an exciter assembly that cycles between generating at leastfirst, second, and third magnetic fields (e.g., first, second, third,fourth, fifth, sixth, seventh, and/or eighth magnetic fields) forcausing a tag to generate a signal, wherein the exciter assemblycomprises A) a base substrate, B) a first exciter coil attached to thebase substrate, wherein current in the first exciter coil travelsclockwise when the first, second, and third magnetic fields aregenerated. In some embodiments, the exciter further comprises C) asecond exciter coil attached to base substrate, wherein current in thesecond exciter coil travels clockwise when the first and second magneticfields are generated, and travels counterclockwise when the thirdmagnetic field is generated. In some embodiments, the exciter assemblyfurther comprises D) a third exciter coil attached to the basesubstrate, wherein current in the third exciter coil travels clockwisewhen the first and third magnetic fields are generated, and travelscounterclockwise when the second magnetic field is generated. In someembodiments, the exciter assembly further comprises E) a fourth exciterattached to the base substrate, wherein current in the fourth excitercoil travels clockwise when the first magnetic field is generated, andtravels counterclockwise when the second and third magnetic fields aregenerated.

Exciter coils, for example, may be wound using Litz wire to minimizeresistive losses due to the skin effect that occurs as frequencyincreases. The number of turns is generally chosen to maximize coil “Q”(the ratio of inductance/resistance). An exemplary coil example is 63turns of Litz wire comprised of 100 strands of 38 AWG wire. Inductanceof an individual coil measures about 1.1 mH and Q (ratio of inductivereactance to resistance) measures over 500 at 134.5 KHz. Other coilconstructions using other wire with different values of inductance and Qmay be used. However, it is generally desired to keep “Q” as high aspossible to minimize resistive losses that result in loss of efficiencyand greater thermal heating.

In some embodiments, provided herein are systems and devices comprising:a) a base substrate, b) a first exciter coil attached to the substrateand configured to generate a magnetic field for causing a tag togenerate a signal, and c) a balun circuit electrically linked to thefirst exciter coil. In some embodiments, the systems and devices furthercomprise a second exciter coil attached to the substrate and configuredto generate a magnetic field for causing a tag to generate a signal, andc) a balun circuit electrically linked to the second exciter coil. Insome embodiments, the systems and devices further comprise a thirdexciter coil, or a third and fourth exciter coil, attached to thesubstrate and configured to generate a magnetic field for causing a tagto generate a signal, and c) a balun circuit electrically linked to thethird exciter coil or a third and fourth exciter coil.

In particular embodiments, the second exciter coil, the second and thirdexciter coil, or each of the second, third, and fourth exciter coils areoperatively connected to a switch that controls the direction of currentthrough a coil. In certain embodiments, each switch comprises a relayelement, a PIN diode, a Field Effect Transistor, or other solid-stateswitching device. In particular embodiments, each switch additionallyswitches at least one capacitor (e.g., two capacitors) into the circuitto keep the resonant frequency of the series combination of excitercoils constant regardless of the change in overall coil inductance thatresults from changing coil polarity.

The inductance of an exemplary exciter coil system measures 1.1 mH withQ>500 for each individual coil. The inductance of the series combinationcoils, such as of 4 coils (e.g., as shown in FIG. 4A) varies withpolarity (current direction) of the coils because of the interaction ofthe magnetic flux produced by each coil. The inductance of the seriescombination of all 4 exemplary coils measures 3.9 mH with Q=435 for thecurrent direction depicted in FIG. 5 where all coils have currentflowing in the clockwise direction. The inductance of the seriescombination of all 4 exemplary coils measures 4.6 mH with Q=500 for thecurrent direction depicted in FIG. 6 where coils A and B have current inthe clockwise direction and coils C and D have current flowing in thecounterclockwise direction. The inductance of the series combination ofall 4 exemplary coils measures 4.3 mH with Q=473 for the currentdirection depicted in FIG. 7 where coils A and C have current in theclockwise direction and coils B and D have current flowing in thecounterclockwise direction. This variation in total inductancenecessitates switching in appropriate compensation capacitors when thecoil polarity is changed.

In some embodiments, the components of the relay or switch andassociated capacitors may be placed on a ceramic substrate to providesecure mounting, excellent dielectric properties, and also serve as aheat spreader to reduce localized heating of individual components.

In some embodiments, the systems and devices further comprise: aplurality of witness coils or witness station assemblies attached to thesubstrate and configured to detect the signal from the tags. In someembodiments, the witness coils are placed such that the axis of the coilis co-planar with the central plane of the exciter coil(s). In thisplane, the magnetic flux produced by the exciter is orthogonal to thesensing axis of the witness coils for every combination of coil currentdirection described previously. The orthogonal exciter current does notinduce a signal into the witness coils and thus provides isolationbetween the exciter coil and witness coils. This isolation is generallyneeded to achieve the needed system dynamic range so that the very weaktag signal may be detected in the presence of the very large excitermagnetic field. This isolation is also important because crosstalkbetween the exciter coil and witness coils would otherwise greatlyimpede navigation because the crosstalk term would contributesignificant signal arising from the same magnetic dipole (the exciter)to all witness coils and therefore the witness coils would lose theirspatial independence. An additional point is that the presence of thez-oriented exciter significantly distorts the z-component of the tag(and emitter) magnetic field, making it less useful for navigation.

In further embodiments, the plurality of witness coils, or plurality ofwitness station assemblies, comprises six to thirty witness coils (e.g.,6 . . . 9 . . . 12 . . . 20 . . . or 30). In additional embodiments, theplurality of witness coils: i) are located on opposing sides of saidbase substrate, but not adjacent to said opposing sides, and/or ii) areeach positioned to alternate opposite orientation along x and y axeswith respect to other witness coils. This positioning minimizescrosstalk between witness coils and thereby reduces the degree thatcrosstalk compensation that is applied (e.g., by a mathematic solversoftware).

In some embodiments, the systems and devices further comprise aplurality of printed circuit boards, wherein each of the plurality ofwitness coils is operably linked to one of the plurality of circuitboards. In certain embodiments, each circuit board comprises at leasttwo capacitors and at least one balun circuit. In particularembodiments, the systems and devices further comprise the linked tags.

In certain embodiments, the systems and devices further comprise a baluncircuit that is electrically linked each of the at least one excitercoils. In further embodiments, the systems and devices further comprisea cable bundle that is electrically linked to the balun circuit. Inadditional embodiments, the systems and devices further comprise aplurality of witness coils attached to the substrate and configured todetect the signal from the linked tags, wherein the plurality of witnesscoils are electrically linked to the cable bundle.

In some embodiments, the systems and devices further comprise at leastone self-test emitter. In other embodiments, the systems and methodsfurther comprise a top cover, wherein the top cover mates with the basesubstrate to enclose each of the exciter coils therein.

In other embodiments, the systems and devices further comprise a systemelectronics enclosure which is configured to provide a signal to theexciter coil(s). In other embodiments, the center of each of the excitercoils is separated from each other by at least 5 centimeters (e.g., 5 .. . 10 . . . 15 . . . 25 . . . 100 . . . 1000 cm). In other embodiments,the center of each of the exciter coils is separated from each other by2-5 times the largest dimension of the coils themselves. In certainembodiments, the fourth exciter coil is positioned next to the secondexciter coil, and wherein the third exciter coil is positioned next tothe first exciter coil and diagonal from the second exciter coil.

In some embodiments, provided herein are methods comprising: a)positioning the systems or devices disclosed herein below or near apatient that has at least two linked tags located therein, and b)activating the system or device such that a magnetic field is generated,thereby causing the each of the linked tags to generate a signal.

In some embodiments, provided herein are systems and devices comprisinga witness station assembly, wherein the witness station assemblycomprises: a) a witness coil, wherein the witness coil comprises: i) ametal core having a coil-free proximal end, a coil-free distal end, anda central region, and ii) coil windings wound around the central regionof the metal core, b) first and second witness coil brackets, and c)first and second elastomeric parts, wherein the coil-free proximal endof the metal core is secured between the first witness coil bracket andthe first elastomeric part, and wherein the coil-free distal end of themetal core is secured between the second witness coil bracket and thesecond elastomeric part. In certain embodiments the systems or devicesfurther comprise a remote activating device (e.g., as described herein),wherein the remote activating device comprises at least one excitercoil. In further embodiments, the systems and devices further comprise:an exciter assembly (e.g., as described herein), wherein the exciterassembly comprises at least one exciter coil.

In further embodiments, the first and second witness coil brackets eachcomprises at least one adjustment part (e.g., two adjustment screws). Insome embodiments, the at least one adjustment part comprises at leastone screw and/or at least one rod. In other embodiments, the witnessstation assembly further comprises an electronics part electricallylinked to the witness coil. In other embodiments, the electronics partcomprises at least one capacitor and/or at least one balun circuit. Infurther embodiments, the electronics part comprises a printed circuitboard.

In certain embodiments, the witness station assembly further comprises afaraday shield. In other embodiments, the witness station assemblyfurther comprises: i) an electronics part electrically linked to saidwitness coil, and ii) a faraday shield. In additional embodiments, thefirst and second elastomeric parts comprise a material selected from: anelastomer polymer and a spring.

In some embodiments, the metal core comprises a ferrite core. In otherembodiments, the metal core has a diameter of 4 to 25 mm (4 . . . 8 . .. 12 . . . 14 . . . 16 . . . 25 mm). In certain embodiments, the metalcore has a length of 15 to 75 mm (e.g., 15 . . . 30 . . . 45 . . . 58 .. . 75 mm). In particular embodiments, the coil windings comprise metalwire. In other embodiments, the metal wire is wound around said metalcore 150-300 times. In further embodiments, the first and second witnesscoil brackets each comprises a notch configured to fit the wire-freeproximal end and/or the wire-free distal end of said metal core.

In particular embodiments, provided herein are devices and systemscomprising: a) an attachment component (e.g., a sheath) configured to beattached to a hand-held medical device with a device tip, wherein theattachment component comprises: i) a proximal end, ii) an angled distalend, wherein the angled distal end comprises a distal end openingconfigured to allow the device tip, but not the remainder of the medicaldevice, to pass therethrough, and iii) a main body stretching betweenthe proximal end and the angled distal end, and b) first and secondlocation emitters attached to the attachment component.

In certain embodiments, the angled distal end has an angle of at least35 degrees with respect to the longitudinal axis of the attachmentcomponent (e.g., at least 35 . . . 45 . . . 65 . . . 85 . . . or 95degrees). In some embodiments, the angled distal end has an angle ofabout 90 degrees with respect to the longitudinal axis of the attachmentcomponent. In further embodiments, the first and second locationemitters are attached to the main body of the attachment component(e.g., spaced apart).

In other embodiments, systems and devices further comprise: c) a displaycomponent housing, wherein the display component housing is attached to,or attachable to, the proximal end of the attachment component. Inadditional embodiments, the systems and devices further comprise adisplay component attached to the display component housing, wherein thedisplay component comprises a display screen (e.g., LCD screen) fordisplaying the location of an implanted tag in a patient relative to thedevice tip on a medical device. In other embodiments, the displaycomponent housing comprises a cable management component. In additionalembodiments, the display component housing comprises a housing taperedconnection. In further embodiments, the proximal end of the attachmentcomponent comprises a proximal tapered connection.

In other embodiments, the devices and systems further comprise first andsecond location emitter wire leads, wherein the first location emitterwire lead is electrically linked to the first location emitter (e.g.,small coil), and the second location emitter wire lead is electricallylinked to the second location emitter (e.g., small coil). In otherembodiments, the systems and devices further comprise: c) an adhesivestrip sized and shaped to cover at least 50% (e.g., 50% . . . 75% . . .90%) of the attachment component main body, and configured to adhere theattachment component to the medical device. In certain embodiments, thesystems and devices further comprise: c) the medical device. In otherembodiments, the medical device comprises an electro-cautery surgicaldevice.

A. Addressing Variable Alignment of an External Coil (e.g., Tag Coil)with the Exciter Assembly

In some embodiments, the exciter is configured to provide power to atag, independent of the alignment of the coil of the tag with theexciter. For example, in some embodiments, power transfer to a tag maybe dependent on the relative orientation of the exciter magnetic fieldto the tag. In some such embodiments, absent a corrective measure, thetag may only collect power from the portion of field aligned to thetag's coil (e.g., a ferrite-core coil contained in the tag). This issuecould be resolved by including multiple exciters capable of producingall three orthogonal directions of the magnetic field. This, however,leads to a thicker assembly and prevents both rejection of primaryexciter coil (e.g., located in the exciter assembly) to sensing coilcoupling (also located in the exciter assembly) (see section B below)and rejection of secondary field coupling between the tags/emitters andexciter coil that subsequently couple to the sensing coils and impairlocalization of the tags or emitters (see section C below). To addressthis challenge, provided herein are configurations of the exciterassembly that provide a mechanism of changing the orientation of themagnetic field with exciter coils that can be deployed in only onemagnetic direction.

In some embodiments, this is accomplished by having multiple coils inthe exciter assembly (see, e.g., FIG. 4A), and setting the direction ofcurrent within each coil to either clockwise or counterclockwise (see,e.g., FIGS. 5-7 ). In some embodiments, the coils are connected inseries so that the same current is running in each. In some embodiments,a coil layout comprises four coils in two rows, centered at (X1, Y1),(X1, Y2), (X2, Y1), and (X2, Y2) coordinates with three sets of currentflow configurations: Configuration 1: all current clockwise to simulatean exciter coil aligned with its plane normal to the Z axis;Configuration 2: coils centered at (X2, Y1), (X2, Y2) running currentcounter-clockwise to simulate an exciter coil aligned to the X axis; andConfiguration 3: coils centered at (X1, Y2), (X2, Y2) running currentcounter-clockwise to simulate an exciter coil aligned to the Y axis.

Any number of other coil configurations may be employed. For efficiency,it is desired (although not required) to minimize the number ofcomponents and overall complexity of the design. However, in someembodiments, it may be desirable to have more than four coils (e.g., 6,8, 10, 16, etc.) in the exciter assembly to provide more flexibility forchanging field directionality, albeit at the expense of systemcomplexity.

Tuning of the coils in the exciter assembly for each configurationrequires less change between configurations when the same current isflowing through all the coils in every configuration. This is becausethe effect of one exciter coil on the others is dependent on the stateof the first exciter coil (open circuit, current-carrying, etc.).

To provide optimal performance, the area of the exciter coils should bemaximized, and the distance between the centers of the coils should bemaximized. A larger area coil provides a higher field for the sameapplied current. Coils separated by larger distances provide a largerdirectional change for Configurations 2 and 3.

FIG. 3 provides an exemplary schematic of a four-coil exciter assemblyin some embodiments of the invention, with the four coils labeled CoilA, Coil B, Coil C, and Coil D (see FIG. 4A).

For medical uses, where the exciter assembly is provided in a flatplanar mode (e.g., pad) beneath a patient, a clinically preferred systemgeometry entails that all four coils are placed very close to eachother. As a result, the magnetic coupling between each coil varies withindividual coil polarity and therefore the total inductance of all fourcoils in series varies with coil polarity combinations. Thus, optimalperformance will necessarily balance competing factors. To compensatefor this, in some embodiments, a system of switching is employed inwhich additional series capacitive reactance is inserted when the totalinductance is increased so that the tuning center frequency ismaintained at the desired excitation frequency. In a preferredembodiment shown in FIG. 3 , relays are utilized for switching.

Other embodiments may employ solid state switching approaches such asPIN diodes. Any suitable mechanism that achieves the switching may beemployed.

In some embodiments, the centers of the coils are separated by 10 . . .50 . . . 100 . . . 500 . . . or 1000 cm. In some embodiments, each coilis from 25 . . . 625 . . . 2500 . . . 62,500 . . . or 250,000 cm² inarea. The largest total series capacitance is needed for a conditionwhen all four coils have the same polarity. In some embodiments, thisseries capacitance is distributed equally among all four coils, balancedon each side of the switching relay as shown in FIG. 3 . Distributingcapacitance this way keeps the contact voltage present at the switch toa minimum. Otherwise, the high “Q” of the coils could result inexcessively high voltage, exceeding 10 KV for some configurations,present at the switches and interconnects.

Additional capacitance useful for maintaining a desired resonantfrequency as described above (e.g., adding capacitors in series toreduce the capacitance) is switched in by the polarity switching relayor a separate switch that may be energized when needed. In someembodiments, this capacitance is distributed among the polarityswitching relays to both minimize terminal voltage and minimize commonmode coupling by achieving best symmetry.

In some embodiments, each capacitance element is comprised of multiplecapacitors to minimize the voltage across each capacitor to ensure thevoltage capability of the capacitors is not exceeded and to minimizeheating due to losses that might otherwise cause the resonant frequencyto drift.

In some embodiments, a balun is incorporated as close as possible to theexciter coils (see Section D below and FIG. 3 ). The balun describedbelow accomplishes common mode rejection to reduce or eliminate electricfield generation and also provides an impedance transformation tooptimally match the coil assembly impedance to that of the transmissionline and power amplifier. In some embodiments, the primary (amplifierside) of the balun has 8 turns and the secondary (coil side) has 4turns, thus providing a 4 to 1 change in impedance that nicely matches,for example, a 50-ohm generator output impedance to a 12-ohm coilimpedance at resonance. Other turns ratio may be employed for optimalimpedance transformation to other characteristic impedance transmissionlines and amplifiers.

FIG. 3 provides an exemplary embodiments of the coil system employed inthe exciter assembly. In this figure, a plurality of capacitors isidentified by number (e.g., C1, C5, C11, C40 etc.; pF (picofarads)) andtheir relative position to Coils A, B, C, and D (see, e.g., FIG. 4A). Abalun with a 7:4 turn ratio is shown (Balun transformer ratio matchesimpedance to 50 Ohms, employing 7:4 ratio, with 7 turns on the 50 ohmside and 4 turns on the coil side). The system may be configured oradjusted to optimize performance based on the manner in which the coilsare utilized. For example, as shown in the exemplary embodiment in FIG.3 :

-   -   Field: Z-plane (++++) capacitors C9 and C10 are 25,600 pF        (20,000 in parallel with 5,600 pF);    -   Field: X-plane (+−+−) capacitors C19 and C20 are 27,235 pF (used        27,000 pF in parallel with series combination of (2) 470 pF        capacitors);    -   Field: Y-plane (++−−) capacitors C29 and C30 are 6,050 pF (2,700        parallel with 3,300 pF in parallel with series combination        of (2) 100 pF capacitors);    -   Common (all fields): capacitors C39 and C40 are 9,000 pF        (parallel combination of (3) 3,000 pF capacitor); and    -   C39 and C40 capacitors (value XY-fixed) are 9,000 pF (18,000 pF        in series with 18,000 pF; could be 9,220 pF; 8,200 in parallel        with 820 pF or other combinations; total voltage is 660 Vrms).

Other specific values of capacitance may be utilized to provide thedesired resonance frequency or frequencies with different values ofinductance that may result from different coil constructions.

B. Addressing Exciter Field Strength Near Sensors

The exciter field strength used to power the tags, in general, is closeto the exciter in order to create a large volume in which a tag or tagscan be powered. This field is much larger than the field provided by thetag or tags or the emitters associated with a surgical tool (the tagsand emitters collectively and individually referred to herein as “thebeacons”). Also, since a single excitation assembly device is preferredto both provide excitation and sensing, the sensing components should bein close proximity to the exciter components. Therefore, the magneticfield sensors would normally sense a magnetic field at the exciterfrequency that is very large, on the order of 160 dB or larger than thesignals of interest (from the beacons).

This issue can be partially resolved by means of electronic filters.However, the rejection capabilities of these filters are limited, theyare expensive, and they are physically large. Filters may be active orpassive. However, active electronic filters have an inherent noise floorthat limits dynamic range and filtering effectiveness for this very highdynamic range situation so passive filters may be employed in someembodiments.

An alternative (or additive) solution takes advantage of the coil systemdescribed in Section A above. In such embodiments, one can reduce theexciter field pickup by the sensors by taking advantage of the vectornature of the magnetic field. In some embodiments, an exciter coil withan orientation generating only magnetic flux substantially perpendicularto the X-Y plane containing the sensing coils is selected. In someembodiments, ferrite-core coils, which are also highly directional innature, are then aligned to that plane, such that magnetic fluxorthogonal to the plane is not sensed. This produces rejection of theexciter field by more than 40 dB. In a preferred geometry, greater than70 dB of isolation has been achieved for all sensing coils in all threepolarity configurations described above. Both the height and tilt ofeach witness coil is adjusted to achieve the alignment needed to achievethis level of isolation for all three coil polarity conditions.Isolation is typically measured using a Vector Network Analyzer byconnecting the exciter coil to port 1 and a specific witness coil toport 2. The magnitude and phase of S₂₁ is then measured at the receivefrequency. In a preferred embodiment, the receive frequency chosen is130.2 KHz.

In such embodiments, the system therefore uses one magnetic fielddirection for excitation, and the two remaining directions (orthogonalto the excitation direction) for sensing. In other embodiments, one canuse two orthogonalities for excitation and one orthogonality forsensing. However, it may be preferable to use two orthogonalities forsensing to provide faster estimates of the beacon position(s).

C. Addressing Exciter/Beacon Coupling

In some embodiments, the exciter is a highly resonant coil. Because, insome embodiments, the beacon's frequency is close to the resonantfrequency of the exciter, a portion of the beacon's AC magnetic fieldaligned to the exciter coil orientation may induce current flow in theexciter and therefore produce a magnetic field in the exciter coilorientation at the beacon frequency. This effect distorts the originalfield from the beacon, making it more difficult to localize the beacon.In a clinically preferred geometry, this distortion masks the truelocation of the beacon such that navigation may become difficult orimpossible.

This coupling can be diminished by choosing a different beacon frequencyless close to the exciter resonance. However, because, in some preferredembodiments, the beacons utilize a single ferrite core RF coil for bothreception and transmission, the available bandwidth is limited.

Using the exciter configuration described in Sections A and B above,instead, since the sensing system comprised of sensing coils is orientedorthogonal to the exciter coil, the distorted field is not sensed. Inother words, distortion is limited to the magnetic field direction thatis substantially aligned to the exciter coil, which is orthogonal to thesensing system. The true location of the beacon is thus no longer maskedby the field distortion produced by the exciter current flow at thebeacon frequency so accurate navigation is achievable without artifact.

D. Addressing Electric Field Magnitude Produced by the System

The exciter and associated circuitry should be designed to minimize theelectric field magnitude produced by the system. If produced, electricfields can couple capacitively into the sensing system and degradesystem accuracy. Electric fields also interact with the patient and theenvironment much more significantly than magnetic fields.

In some embodiments, this challenge is addressed by incorporating abalun as close as possible to the exciter coils. The balun, which canalso act as an impedance transformer, minimizes electric field byeliminating asymmetric current flow with respect to ground. Another wayto think of this is that the balun eliminates common mode coupling. Insome embodiments, on the exciter side of the balun, the circuit designand layout should be as symmetric as possible to maintain balance.

In addition to reducing electric field effects, the transformer allowsoff the shelf 50-ohm coaxial transmission line to be used withoutmismatch. This scales transmission line voltage and current to optimallytransmit power to the exciter assembly with the best efficiency and thesmallest, most flexible, coaxial cable.

E. Identifying and Managing Locations of Multiple Beacons

In accordance with the methods described herein, two or more beacons(e.g., tags, emitters associated with one or more surgical devices, orother objects whose location, position, relative position, or otherspatial information desired) are employed. The two or more beacons (e.g.tags) are linked together by a linker (e.g. “linked tags”). In someembodiments, each beacon generates the same frequency. Such embodimentsmay be advantages because the signal strength could be up to 2× larger(assuming two tags are used, 3× larger if three tags are used, 4× largerif 4 tags are used, etc.) than with one beacon alone. Accordingly, suchembodiments may be useful in large patients, wherein tissue volume ofthe patient would otherwise limit the ability to detect a signal from asingle beacon.

In some embodiments, each beacon generates the same frequency and thetwo signals can be deconvoluted to improve overall accuracy indetection. In some embodiments, the tags are programmed to respond withan offset frequency compared to the frequency of the stimulatingfrequency. In some embodiments, the tags are programmed to respond withan offset frequency and a stable phase locked to the phase of thestimulating signal. This strategy allows the response signal(s) to beeasily decoupled from the stimulating signals. In particular, a stablephase locked to the stimulating signal allows for precise localizationof the signal of each of the at least two linked tags. In someembodiments, each of the two or more tags generates the same frequency,but are programmed to have a set phase offset. In some embodiments, eachbeacon generates the same frequency, but the phase of each beacon can bea random factor of 11.25 degrees, which can be exploited to deconvolutethe two signals.

In some embodiments, each different beacon (e.g. tag) generates a uniquefrequency, spectrum of frequencies or otherwise distinguishable signal.In some such embodiments, a hunting algorithm is employed to identifythe spatial information of one or more of the beacons. In someembodiments, the optimal exciter polarity and power level is identifiedfor each beacon (e.g., accounting for any relative orientation of beaconto the exciter) by cycling the exciter through different planes. Basedon this information, an optimal exciter pattern is calculated tomaximize the quality of the procedure and accuracy of informationconveyed to a user (e.g., treating physician). In some such embodiments,a first optimal pattern is utilized to provide spatial information abouta first tag and a first portion of a procedure is conducted. Next, asecond optimal pattern (which may be the same or different) is utilizedto provide spatial information about a second tag and a second portionof a procedure is conducted. Further cycles may be conducted foradditional tags. Alternatively, the exciter pattern (polarity and power)may cycle between multiple, different optimal patterns during aprocedure to provide near real-time optimal spatial information ofmultiple beacons. In some such embodiments, rapid switching of coilpolarity in the emitter is employed to simultaneously ornear-simultaneously power two or more beacons.

F. Exemplary Protocol

The technology is not limited by the mode of tag placement and a widevariety of placements techniques are contemplated including, but notlimited to, open surgery, laparoscopy, endoscopy, via endovascularcatheter, etc. The tags may be placed by any suitable device, including,but not limited to, syringes, endoscopes, bronchoscopes, extendedbronchoscopes, laparoscopes, thoracoscopes, etc. An exemplary protocolis provided below.

A patient previously identified as having a breast tumor is admitted toa medical facility. The patient is initially sent to radiology. Theradiologist examines prior imaging information identifying the targettumor. The subject is administered a local anesthetic, usually lidocaineor a derivative, using a needle introduced percutaneously. The subjectis positioned in an imaging device, generally either ultrasound,conventional mammography, or a stereotactic unit. The location of thetumor is determined. An introducer needle (usually 6-gauge) is insertedeither into or just proximal to the tumor and a biopsy needle is placedthrough the introducer needle and a specimen is obtained using a varietyof methods (suction, mechanical cutting, freezing to fix the position ofthe tissue followed by mechanical cutting). After the specimen isobtained and sent for pathologic examination, a 6-20 gauge tag deliveryneedle is inserted into the coaxial introducer needle to the tissue withthe distal open end positioned at the lesion. Two linked tags areinserted into the proximal end of the delivery needle and delivered byplunger through the opening at the distal end of the needle and into thetissue. Likewise, the tags could have been pre-positioned at the distalend of the delivery needle. Proper location of the linked tags isconfirmed via imaging. The delivery needle is withdrawn, leaving thetags in place in the breast tissue.

This type of procedure can be performed in an analogous manner invirtually any body space, organ, or pathologic tissue with the intent oflocalizing that tissue or space for further diagnosis or treatment ofany kind. Areas of particular interest include but are not limited tothe following organs, and disease processes that take place within them:brain, skull, head and neck, thoracic cavity, lungs, heart, bloodvessels, gastrointestinal structures, liver, spleen, pancreas, kidneys,retroperitoneum, lymph nodes, pelvis, bladder, genitourinary system,uterus, ovaries, and nerves.

In some embodiments, during surgery, the patient is placed onto anoperating table with the surgical area exposed and sterilized. Thesurgeon is provided with the imaging information showing the location ofthe target tissue (e.g., tumor) and tags. An incision is made at thelocation of the entry point of the placement needle. The remoteactivating device is placed in proximity to the tissue to activate thetags. The detection component comprising the witness stations (e.g., asshown in FIG. 4A) detects a signal from the tags and allows the surgeonto guide the direction of the medical device toward the tumor. Once thetumor is localized, the surgeon removes the appropriate tissue and,optionally, removes the tags.

In some embodiments, the system finds use in surgery with the tagsplaced as fiducials on or in the body. The relative position of the tagsand any surgical instruments is located using the electromagnetic field.This information is communicated to a physician in real-time using avariety of methods including by not limited to visual (computer screens,direction and depth indicators using a variety of methods, hapticfeedback, audio feedback, holograms, etc.), and the position of theinstruments displayed on any medical images such as CT, MRI, or PETscans in 2D or 3D. This data finds use to guide the physician during aprocedure, or is used as a training method so that physicians canperform a virtual procedure. Such system may be integrated into orprovide alternative approaches to existing surgical systems, such as theSTEALTH system (Medtronic) for applications such as neurosurgeries.

In some embodiments, information about the location of the tags or thesurgical paths or routes to the tags is conveyed to a surgeon or otheruser in a manner that comprises one or more augmented reality or virtualreality components. For example, in some embodiments, a surgeon wears oraccesses a virtual reality device (e.g., goggles, glasses, helmet, etc.)that shows a partial or complete virtual image of the patient orsurgical landscape. Tag position information collected and calculated bythe systems described herein are represented by one or more visualcomponents to the surgeons to assist in accurate targeting of the tag ortags. For example, the tissue containing the linked tags may berepresented with a virtual image of the tags location shown. Likewise,in some embodiments, a surgical pathway is visually presented, forexample, as a colored line to be followed. In some embodiments employingaugmented reality features, a display, presents a graphical or videocapture of the patient representative of what the surgeon wouldvisualize if the monitor were not present and overlays one or moreaugmented features on the display. The graphical or video display datamay be captured by one or more cameras in the surgical field. Theaugmented features include, but are not limited to, a representation ofthe location of the tags in the target tissue, a projected surgicalpath, a target point to which the surgeon aligns the tip of the surgicaldevice, a simulated surgical margin zone to treat, arrows or otherlocation indicators that recommend movement if the optimal pathway isdeviated from, or the like.

An exemplary exciter assembly 250 is shown in FIGS. 4, 5, 6, and 7 .This exciter assembly, as shown in FIG. 1 , can be positioned under themattress of a patient lying on a surface, such as an operating table ormattress. The exemplary exciter assembly in these figures provides theexcitation signal, via four exciter coils 150, for the tag(s) in thepatient. The exemplary exciter assembly in FIG. 4A provides a pluralityof witness coil assemblies (aka witness station assembly) 161, each witha witness coil 160, in order to detect the signal from implanted tag(s)and the tags in the attachment component that is attached to thesurgical device. The exciter assembly is composed of a base substrate140 to which other components are generally attached or integrated into.The base substrate is composed of any suitable material, which may be,for example, polycarbonate or the like and is typically nonmagnetic andnon-electrically conducting. Not pictured in FIG. 4A is a top cover 230(see FIG. 8 ) that mates with the base substrate, enclosing all theinternal components therein. The top cover is composed of any suitablematerial, including Kevlar and/or other rigid materials, again typicallynonmagnetic and non-electrically conducting. Foam or other type ofpadding may be included on top of the top cover.

Attached to the base substrate are four large exciter coils 150, whichare labeled “Coil A,” “Coil B,” “Coil C,” and “Coil D,” in FIG. 4A. Eachexciter coil 150 can be wound around four exciter coil mounts 155. Incertain embodiments, the exciter coils are not wound in any particularform and instead employ wires that bond to themselves to create the coilshape. While not shown in FIG. 4A, in certain embodiments, coil covers(e.g., plastic coil covers) are situated over each of the four excitercoils. Between the four exciter coils, generally centrally located, is alarge central balun circuit 180.

On the interior of exciter coils B, C, and D is a switch 190. The switch190 contains a component, such as a relay or multiple PIN diodes (e.g.,at least four PIN diodes), or filed effect transistor, that controls thedirectionality of the current (clockwise or counterclockwise) in therespective exciter coils. In the particular embodiment in FIG. 4A,excited Coil A does not have a switch 190 as the direction in this coilis not changed. The switch 190 is linked to difference capacitorsemployed to correctly match the different inductance resulting fromchanging the directionality of current flow. If a relay(s) (e.g., fourSPST, two SPDT type or one DPDT) is employed in the switch, it generallydirects an input to one of two outputs. If multiple PIN diodes areemployed (to create relay function) in the switch 190, this provides avery high impedance when “off” and low impedance when “on.” Each switch190 also is linked to one or more capacitors to modify the capacitancethat, along with the exciter coil inductor, forms the resonant circuit.This is necessary because the effective total series inductance of allexciter coils changes when the current flow direction is changed. Alsoon the interior of Coils A-D are a pair of capacitor assemblies 195,composed of a central capacitor 197, flanked by metal leads 199. Incertain embodiments, the metal leads 199, are affixed to ceramic heatspreaders, in order to dissipate heat that builds up during operation.

In operation, the exciter assembly in FIG. 4A is configured, in certainembodiments, to cycle between three configurations, called Configuration1 (shown in FIG. 5 ), Configuration 2 (shown in FIG. 6 ), andConfiguration 3 (shown in FIG. 7 ). In Configuration 1, as shown in FIG.5 , the current from all four exciter coils is clockwise in order tosimulate an exciter coil generally aligned with its plane normal to theZ axis. In Configuration 2, as shown in FIG. 6 , the current from Coil Aand Coil B is clockwise, while the current from Coil C and Coil D iscounterclockwise, in order to simulate an exciter coil generally alignedto the Y axis. In configuration 3, as shown in FIG. 7 , the current fromCoil A and Coil C is clockwise, while the current from Coil B and Coil Dis counterclockwise, in order to simulate an exciter coil generallyaligned to the X axis. Although this is a preferred embodiment, othercombinations of coil polarities with other values of additional seriescapacitance may be advantageous for certain tag orientations. Forexample, the current in coil A, instead of being clockwise, could becounterclockwise, and then all of the other 3 coils (Coils B, C, and D)could have the current flow as shown in FIG. 5, 6 , or 7, or the other 3coils (Coils B, C, and D) would have the opposite current flow as shownin FIGS. 5, 6, and 7 . In other embodiments, the current arrangement isas shown in FIG. 6 , except the current in Coil B is counterclockwise,and the current in Coil D is clockwise. Every different combination ofclockwise and counterclockwise for the Coils A-D is contemplated (i.e.,all sixteen combinations).

The exemplary exciter assembly 250 in FIG. 4A is also shown with twelvewitness station assemblies 161 (each with a witness coil 160). Thetwelve witness coils 160 alternate opposite orientation (along x and yaxes) to reduce crosstalk. In other embodiments, software may also oralternatively be used to reduce cross talk. In certain embodiments,rather than alternating orientation, all of the witness coils pointtoward the center, which would increase crosstalk, but may have theadvantage of shifting the location of inflection points in the witnesscoil signal pickups as a beacon is transitioned across the perimeter ofthe exciter assembly. It is generally preferably for the wires that feedinto the exciter coils not be in close proximity to any of the witnesscoils, to prevent reduction in isolation and noise pickup. In FIG. 4A,the wires from the center balun circuit to each of the four excitercoils are in a location away from the twelve witness coils 160. Also, asshown in FIG. 4A, the witness coils run down the left and right side ofthe exciter assembly, and do not run across the top or bottom of theexciter assembly. Adding witness stations across the top and/or bottomcan cause strong crosstalk to occur. Alternatively, softwareapplications can be used to reduce cross talk if witness coils areplaced in positions that induce crosstalk. The witness coils 160 areheld in place by a pair of witness coil brackets 165.

Next to each witness coil 160 is a printed circuit board 170. Eachprinted circuit board 170 contains capacitors and a small balun circuit.The capacitors, along with the witness coil, are employed to create aresonant circuit. The balun serves to eliminate common mode effects thatwould otherwise make the witness coil assembly susceptible to electricfield interaction. It also may serve as an impedance matching elementthat matches the real impedance of the coil/capacitor resonant circuitto the transmission line characteristic impedance, typically 50 Ohms, byoptimally selecting the number of primary and secondary turns.

The exciter assembly 250 in FIG. 4A is also shown with a pair ofself-test emitters 220. These self-test emitters 220 are present suchthat one can apply known signals and check the response on all witnesscoils. If a witness coils does not show the expected signal, itindicates a system problem, or could indicate the presence of aninterfering magnet or piece of metal which is distorting the field anddegrading overall localization accuracy. It is noted that anotherself-test that can be employed is to generate a signal on the excitercoils that is normally applied to one of the emitters on the attachmentcomponent (e.g., sheath on hand held surgical device). By measuring thesignal passed from the exciter to each witness coils, one can confirmthe level of isolation between them. In still another self-test, asignal may be applied to each witness coil individually and theremaining witness coils may be used to detect the signal. In otherembodiments, field witness coil crosstalk may also be measured this wayand used to calibrate the system.

FIG. 4A shows various wire connections between the various components ofthe exciter assembly. Each witness coil 160 is attached to a coaxialcable which is connected to the system electronics enclosure (labelled“controller,” 210) via the cable bundle 200. The exciter signal comesfrom the cable bundle 200 into the central balun circuit 180. Fromthere, wires carry the signal to the switches 190 and/or capacitorassemblies 195. The system electronics enclosure (controller 210)performs signal processing (e.g., filtering, mixing, amplification,digitization, and demodulation of multiple frequency ‘channels’) on thewitness coil signals. Generally, no A/C main power is applied to thewitness coils.

In regard to the capacitors employed in each capacitor assembly 195, andin the printed circuit boards 170, in general, the capacitors are chosento be COG/NPO type where the capacitance value does not change withtemperature, so that the resonant frequency of the exciter does notchange with temperature. The capacitors also provide a tuning networkwhich can selectively add capacitance in series to change the resonantfrequency, which helps reduce tolerances during manufacturing, as wellas makes it more tolerant of tuning changes due to temperature and otherfactors. In general, all the materials employed should have highdielectric strength and high stability over temperature to preventgeometric changes as the exciter assembly is used and the temperature israised.

An exemplary witness coil assembly (aka witness station assembly) 161 isshown in FIG. 4B. Witness coil assembly 161 includes witness coil twowitness coil brackets 165, which are used to clamp a secure witness coil160 against elastomer 162. The witness coil 160, as shown in FIGS. 4Band 4C, is composed of a metal core (e.g., ferrite core) 166 and coils167 formed from wire. As shown in exemplary FIG. 4C, the metal core 166is composed of a central region 173 (under the wires in FIG. 4C), with awire-free proximal end 171 and a wire-free distal end 172. Only theferrite core (using the proximal and distal ends that are wire-free) isclamped by bracket 165 and elastomer 162 (e.g., to provide bestregistration and eliminate the possibility of damaging the coil windings167 of witness coil 160). The height of each end of witness coil 160 maybe adjusted up or down by adjustment screws 163 (present in each witnesscoil bracket 165) while a restoring force is provided by elastomer 162.Elastomer thickness and durometer is chosen to provide the neededrestoring force over the desired range of adjustment so that theadjustment screws will be easily adjusted yet hold the desired settingonce the optimal position is achieved. Additionally, coil brackets 165each has a “V” or “U” shaped feature that allows them to secure theproximal and distal ends of the metal core 166. This allows, forexample, the brackets 165 to precisely register the witness coil core(e.g., ferrite core) in the desired direction so it cannot rotate aboutan axis perpendicular to the plane containing exciter coils. The witnesscoil assembly 161 also includes a printed circuit board 170 (withcapacitors and balun circuit) and a faraday shield 168. The faradayshield may be composed of conductive material, such as brass or copper.

In certain embodiments, the exciter coil (e.g., as shown in FIG. 4A) isconnected to port 1 of a vector network analyzer or VNA. The witnesscoil output is generally connected to port 2 of the VNA and transmission(S21) is measured and displayed. This measurement is a directmeasurement of the signal present at port 2 resulting from excitationprovided to port 1 and is, therefore, a direct measurement of isolation.The lower S21 (more negative) the better. The more negative S21 thebetter. Typical isolation values (S21) achieved with the generallypreferred embodiment are −70 dB with usable ranges including −50 dB tomore than −100 dB (e.g., the noise floor of the VNA).

In general, to achieve the best isolation between exciter coil andwitness coil for the best accuracy over the largest navigation volume,it is generally important to position the witness coils orthogonal(e.g., precisely orthogonal) to the magnetic flux produced by theexciter coil. FIG. 4A shows such an orthogonal arrangement of the twelvewitness coils. Small offsets to height or tilt of the witness coil fromthis optimal position will generally result in signal coupling to thewitness coil from the exciter coil that undermines isolation.Accordingly, in certain embodiments, the screws (or other connectors) onthe witness coil brackets are employed to make fine adjustments.

FIG. 4C shows an exemplary witness coil 160, including how the coils 167are formed by wire being wound around the metal core in three stages: i)wind direction 1, where wire is wound around most of a first half of themetal core; ii) wind direction 2, where wire is wound over the top ofthe wire wound over the first half, as well as over most of the secondhalf of the metal core; and iii) wind direction 3, where wire is woundback over the wire on the second half. In certain embodiments, 80-140windings (e.g., 80 . . . 90 . . . 112 . . . 140) are on each half of themetal core (e.g., for total of 160-280 windings (e.g., 160 . . . 200 . .. 224 . . . 280). In certain embodiments, the wire is 32 AWG coppermagnet wire with a single layer polyester enamel and bond coat (e.g.,0.011 inches in diameter), and heat is used during wrapping to securewire wraps. In certain embodiments, the metal core is a ferrite corepart number #4077484611 from FAIR-RITE products corporation. In certainembodiments, the metal core (e.g., ferrite core) has a diameter of about10-15 mm (e.g., 10 . . . 12 . . . 14 . . . 15 mm), and is about 30-50 mmin length (e.g., 30 . . . 35 . . . 45 . . . 50 mm). In certainembodiments, the metal core has a diameter of about 12.7 mm and a lengthof about 41.5 mm.

The wire is also connected to the secondary of a small balun transformer(in the printed circuit board, part 170 in FIG. 4B) through two seriescapacitances (e.g., in the printed circuit board), one for each wirefrom the coil. In general, in certain embodiments, the total seriescapacitance is selected to resonate with the inductance of the coil inthe tags, and the turns ratio of the balun transformer may be chosen tomatch the real impedance of the resonant coil/capacitor circuit to thetransmission line (e.g., around 50 Ohms). In certain embodiments, thereal impedance of the resonant coil/capacitor circuit is typically 10 to25 Ohms, but may vary from just a couple Ohms to greater than 50 Ohmsand may be adequately matched by appropriate choice of balun transformerprimary and secondary turns. In addition to its role as impedancetransformer, the balun minimizes any electric fieldgeneration/susceptibility from the witness coil assembly; alternately,it may be thought of as removing common mode effects. To further reducethe electric field susceptibility, the use of a conductive faradayshield 168 over the balun and capacitors is employed. This faradayshield (e.g., Faraday cage) reduces the observed electric field tocomponents under the shield. Typically a Faraday shield is used toreduce the emission of electric fields of components under the shield,in this case it is also reducing the reception of electric fields.

FIG. 8 shows an emitter component 250 with the top cover 230 on. The topcover 230 may be composed of Kevlar or other suitably tough material.The exciter assembly 250 is shown with cable bundle 200 leading therein.

FIG. 9 shows an attachment component 10, with an angled distal end 300that the distal tip 25 of the medical device 20 is inserted through. Thedisplay component 40 is attached to an attachment component control unit310 via attachment component wire 60.

FIG. 10A shows the distal end 25 of a medical device 20 after it isinitially inserted through the angled distal end 300 of attachmentcomponent 10. This view is prior to the attachment component wire 60being inserted into the cable management component 315. FIG. 10B showsattachment component wire 60 prior to being attached to the cablemanagement component 315 of the display component housing 330. FIG. 10Balso shows the housing tapered connection 340 that the proximal endtapered connection 350 of the attachment component 10 is inserted into.The cable management component 315 has two clips that align both theattachment component wire 60 and the medical device wire 50.

FIG. 11 shows an attachment component 10 attached to a display componenthousing 330. The attachment component 10 has a pair of location emitters70, which are linked to location emitter wires leads 72 which are insidetube 360. The location emitters 70 are powered by the wire leads 72 togenerate a signal which is detected by the witness coils. The attachmentcomponent also has an angled distal end 300 with a distal end opening305, which allows the tip of a medical or other device to be insertedtherethrough. The display component housing 330 has a cable managementcomponent 315, composed of a pair of clips for holding the attachmentcomponent wire and the medical device wire.

FIG. 12 shows an exemplary attachment component 10 attached to a displaycomponent housing 330 with a display component 40 located therein. Adisplay cover 370 is shown, which is used to secure the displaycomponent 40 inside the display component housing 330. Also shown is anadhesive strip 380 (e.g., a two sided strip with strong adhesive on bothsides), which is shaped and sized to fit inside the attachment componentand help secure a medical device to the attachment component.

FIG. 13A shows the proximal end tapered connection 350 of the attachmentcomponent 10, which is configured to push-fit into housing taperedconnection 340 of the display component housing 330. FIG. 13B shows aclose up of section A of FIG. 13A, including cable management taperedconnection 317 that is part of cable management component 315 anddesigned to be inserted into tapered connection hole 319 of displaycomponent housing 330. Cable management tapered connection 317 includesa flat part 318 to lock angular position.

FIG. 14 shows an exemplary system for localizing tags that are implantedin a patient. The system is composed of an exciter assembly that emitssignals that activate the tags in the patient. A systems electronicsenclosure is shown as a mobile cart, which delivers signals to theexciter assembly and receives and processes signals from the tag(s) inthe patient and the location emitters in the attachment component.Guidance for a surgeon is displayed on the display component, as well ason a screen on the systems electronics enclosure.

1. A system comprising: a) at least two tags, b) a linker attached tosaid at least two tags; c) a remote activating device that generates amagnetic field within a region of each tag; and d) a plurality ofsensors configured to detect a signal from each tag while each tag isexposed to said magnetic field.
 2. The system of claim 1, wherein thetags are programmed to respond to a signal from said magnetic field withan offset frequency compared to said signal.
 3. The system of claim 1,wherein the tags comprise a non-dielectric resonant antenna capacitor.4. The system of claim 3, wherein the tags comprise a standard thin filmcapacitor or a multi-layer ceramic capacitor.
 5. The system of claim 1,further comprising a wire or line, wherein said wire or line is attachedto, and/or passes through, said linker at two or more points on saidlinker.
 6. The system of claim 5, wherein said wire or line is attachedto, and/or passes through, said linker such that said two or more tagsare held in a first position with respect to each other, and whereinsaid linker is configured to hold said two or more tags in a secondposition when said wire or line is not attached to, and/or does not passthrough, said linker, wherein said second position is different fromsaid first position.
 7. The system of claim 1, wherein the linkercomprises a torsion spring.
 8. The system of claim 1, wherein each ofthe tags is attached to the linker via heat shrink tubing.
 9. The systemof claim 1, wherein said linker is configured to hold said at least twotags in a first position when said tags are present in an insertiondevice.
 10. The system of claim 1, wherein said linker is configured tohold said at least two tags in a second position when present in tissue,wherein at least one of said tags in said second position pointsapproximately in the X dimension, and at least one of said tags pointsapproximately in the Y dimension.
 11. The system of claim 1, whereinsaid at least two tags comprises first, second, and third tags, andwherein, when in said second position: i) said first tag pointsapproximately in the X dimension, ii) said second tag points inapproximately the Y dimension, and iii) and said third tag points inapproximately in the Z dimension.
 12. (canceled)
 13. The system of claim1, wherein the linker comprises plastic.
 14. The system of claim 1,wherein the linker comprises a shape-memory alloy.
 15. The system ofclaim 14, wherein the shape-memory alloy comprises a nickel-titaniumalloy.
 16. The system of claim 15, wherein the nickel-titanium alloy isNitinol 55 or Nitinol
 60. 17. The system of claim 1, wherein the atleast two tags are positioned to form an angle within a range of 15degrees to 40 degrees.
 18. The system of claim 17, wherein the angle is25 degrees.
 19. The system of claim 1, wherein the linker includes agrip that is graspable by a surgical tool.
 20. The system of claim 19,wherein the grip is a sphere.
 21. The system of claim 19, wherein thelinker is positioned within a packaging with a notch that exposes thegrip. 22.-73. (canceled)